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−* Clinically aggressive, mature B cell lymphoma+* Small to medium sized lymphoid cells (monomorphic, except in pleomorphic variant)+* Associated with t(11;14)(q13;q32) and cyclin D1 overexpression in over 95% of cases+ +Obsolete names:+ +*Centrocytic malignant lymphoma (obsolete) <ref>{{Cite journal|last=K|first=Lennert|last2=H|first2=Stein|last3=E|first3=Kaiserling|date=1975|title=Cytological and functional criteria for the classification of malignant lymphomata|url=https://pubmed.ncbi.nlm.nih.gov/52366/|language=en|pmc=PMC2149614|pmid=52366}}</ref>+*Lymphocytic lymphoma of intermediate differentiation <ref>{{Cite journal|last=H|first=Kim|last2=Rj|first2=Zelman|last3=Ma|first3=Fox|last4=Jm|first4=Bennett|last5=Cw|first5=Berard|last6=Jj|first6=Butler|last7=Ge|first7=Byrne|last8=Rf|first8=Dorfman|last9=Rj|first9=Hartsock|date=1982|title=Pathology Panel for Lymphoma Clinical Studies: a comprehensive analysis of cases accumulated since its inception|url=https://pubmed.ncbi.nlm.nih.gov/6948126/|language=en|pmid=6948126}}</ref>+*Mantle zone lymphoma <ref>{{Cite journal|last=Dd|first=Weisenburger|last2=H|first2=Kim|last3=H|first3=Rappaport|date=1982|title=Mantle-zone lymphoma: a follicular variant of intermediate lymphocytic lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/6895860/|language=en|pmid=6895860}}</ref>+*Malignant lymphomatous polyposis+*in situ mantle cell lymphoma (for in situ mantle cell neoplasia)+ +==Epidemiology / Prevalence==+
−*~ 7% of B cell lymphomas <ref>{{Cite journal|date=1997|title=A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project|url=https://pubmed.ncbi.nlm.nih.gov/9166827/|language=en|pmid=9166827}}</ref>
−*Age adjusted incidence: 0.7/100,000 person years in white population in USA <ref>{{Cite journal|last=B|first=Aschebrook-Kilfoy|last2=Db|first2=Caces|last3=Nj|first3=Ollberding|last4=Sm|first4=Smith|last5=Bc|first5=Chiu|date=2013|title=An upward trend in the age-specific incidence patterns for mantle cell lymphoma in the USA|url=https://pubmed.ncbi.nlm.nih.gov/23350889/|language=en|pmid=23350889}}</ref>
−*Median age: 60 years<ref>{{Cite journal|last=Lh|first=Argatoff|last2=Jm|first2=Connors|last3=Rj|first3=Klasa|last4=De|first4=Horsman|last5=Rd|first5=Gascoyne|date=1997|title=Mantle cell lymphoma: a clinicopathologic study of 80 cases|url=https://pubmed.ncbi.nlm.nih.gov/9058729/|language=en|pmid=9058729}}</ref>
−*M:F = 3:1 (range, 1.6-6.8 :1)<ref>{{Cite journal|last=P|first=Lardelli|last2=Ma|first2=Bookman|last3=J|first3=Sundeen|last4=Dl|first4=Longo|last5=Es|first5=Jaffe|date=1990|title=Lymphocytic lymphoma of intermediate differentiation. Morphologic and immunophenotypic spectrum and clinical correlations|url=https://pubmed.ncbi.nlm.nih.gov/2198813/|language=en|pmid=2198813}}</ref>
−
−
−Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
+<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
−
−<span class="blue-text">EXAMPLE:</span> Fatigue
−
−<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
−<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
−*Approximately 70% with stage IV disease at presentation
−**Generalized lymphadenopathy, hepatosplenomegaly and bone marrow involvement
−**40-50% with B symptoms
−** Two subtypes based on clinical presentation:
−*** More aggressive, with SOX11 overexpression (SOX11+disease), nodal presentation (the most common subtype)
−*** More indolent, without SOX11 expression (SOX11-disease), leukemic presentation, and non-nodal disease
−*Peripheral blood:
−**Atypical lymphoid cells: present virtually in all cases by flow cytometry <ref>{{Cite journal|last=A|first=Ferrer|last2=I|first2=Salaverria|last3=F|first3=Bosch|last4=N|first4=Villamor|last5=M|first5=Rozman|last6=S|first6=Beà|last7=E|first7=Giné|last8=A|first8=López-Guillermo|last9=E|first9=Campo|date=2007|title=Leukemic involvement is a common feature in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/17477385/|language=en|pmid=17477385}}</ref>
−***Atypical lymphoid cells can be detected in the peripheral blood in the absence of lymphocytosis
−***Leukemic involvement: 20 - 70% of patients at diagnosis
−***Leukemic involvement is usually a the sign of disease progression
−**Blastoid morphology of the circulating lymphoma cells may mimic acute leukemia
−**A leukemic phase with no or minimal lymph node involvement is possible, [[HAEM5:Leukaemic non-nodal mantle cell lymphoma]]
−***Asymptomatic for long period
−***Splenomegaly
−**Anemia and thrombocytopenia (10%- 40%)
−*Multiple intestinal polyps (lymphomatous polyposis)
−*Progress to blastoid / pleomorphic variant
−**At the time of relapse (~22%)
−<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref>Arber, D.A., et al., ''Hematopathology''. 2017, Philadelphia, PA: Elsevier.</ref></blockquote>
−</blockquote>
−==Sites of Involvement==
−*Lymph node
−*Bone marrow involvement independent of peripheral blood (50 - 90%), peripheral blood (20 - 70%), spleen (~50%), liver (~20%) <ref>{{Cite journal|last=J|first=Wasman|last2=Ns|first2=Rosenthal|last3=Dc|first3=Farhi|date=1996|title=Mantle cell lymphoma. Morphologic findings in bone marrow involvement|url=https://pubmed.ncbi.nlm.nih.gov/8712173/|language=en|pmid=8712173}}</ref><ref>{{Cite journal|last=Ma|first=Vasef|last2=Lj|first2=Medeiros|last3=C|first3=Koo|last4=A|first4=McCourty|last5=Rk|first5=Brynes|date=1997|title=Cyclin D1 immunohistochemical staining is useful in distinguishing mantle cell lymphoma from other low-grade B-cell neoplasms in bone marrow|url=https://pubmed.ncbi.nlm.nih.gov/9291459/|language=en|pmid=9291459}}</ref><ref>{{Cite journal|last=H|first=Samaha|last2=C|first2=Dumontet|last3=N|first3=Ketterer|last4=I|first4=Moullet|last5=C|first5=Thieblemont|last6=F|first6=Bouafia|last7=E|first7=Callet-Bauchu|last8=P|first8=Felman|last9=F|first9=Berger|date=1998|title=Mantle cell lymphoma: a retrospective study of 121 cases|url=https://pubmed.ncbi.nlm.nih.gov/9697885/|language=en|pmid=9697885}}</ref>
−*Frequent extranodal site involvement : gastrointestinal tract, Waldeyer ring, lungs, pleura, skin, CNS
−**CNS involvement may occur mostly at the time of relapse<ref>{{Cite journal|last=Cy|first=Cheah|last2=A|first2=George|last3=E|first3=Giné|last4=A|first4=Chiappella|last5=Hc|first5=Kluin-Nelemans|last6=W|first6=Jurczak|last7=K|first7=Krawczyk|last8=H|first8=Mocikova|last9=P|first9=Klener|date=2013|title=Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network|url=https://pubmed.ncbi.nlm.nih.gov/23616279/|language=en|pmid=23616279}}</ref>
−*Extranodal involvement without lymphadenopathies: 4 - 15%
−==Morphologic Features==
−*Architectural pattern: Diffuse > nodular > mantle zone growth patterns
−**Nodal (> 50% nodular), diffuse growth pattern (< 50% nodular)
−*Cytologic variants: Classic, blastoid, pleomorphic, small cell, marginal zone-like
−*Blastoid and pleomorphic cytologic variants are known as aggressive variants of MCL
−*Classic variant:
−**Small to medium monomorphic lymphoid neoplasm
−**Irregular nuclear border, clumped chromatin and inconspicuous nucleoli
−**No proliferation centers
−**No centroblasts, immunoblasts or paraimmunoblasts
−**Hyalinized vessels
−**Epithelioid histiocytes
−**Follicular dendritic cell (FDC) meshwork
−***Nodular pattern
−****Primary follicle-like pattern
−****Germinal center-like pattern
−***Diffuse pattern
−*Aggressive variants
−**Blastoid: lymphoblast-like in appearance, monomorphic
−***>20 - 30 mitoses per 10 high power fields
−***Resemble lymphoblastic lymphoma
−**Pleomorphic: large cells with irregular nuclear border, cerebriform nuclei, multinucleation, lack of monomorphism
−***Prominent nucleoli and abundant pale cytoplasm
−***Resemble DLBCL
−*Other variants
−**Small cell: small round lymphocytes with more clumped chromatin
−***Resemble CLL
−**Marginal zone-like: abundant pale cytoplasm
−***Resembling marginal zone or monocytoid B cells
−**Lymphoplasmacytic differentiation, some cases <ref>{{Cite journal|last=Kh|first=Young|last2=Wc|first2=Chan|last3=K|first3=Fu|last4=J|first4=Iqbal|last5=Wg|first5=Sanger|last6=A|first6=Ratashak|last7=Tc|first7=Greiner|last8=Dd|first8=Weisenburger|date=2006|title=Mantle cell lymphoma with plasma cell differentiation|url=https://pubmed.ncbi.nlm.nih.gov/16861965/|language=en|pmid=16861965}}</ref>
−*Bone marrow
−**Nodular, interstitial or paratrabecular or combination
−*Peripheral blood (see below)
−**Similar spectrum seen in tissue sample
−**Nucleoli are sometimes more prominent
−*Spleen
−**White pulp nodules involved (enlarged)
−**Variable involvement of the red pulp
−**Residual naked germinal centers
−**Tumor cells: similar monotonous morphology
−**Some cases may show a marginal zone-like area <ref>{{Cite journal|last=Ma|first=Piris|last2=M|first2=Mollejo|last3=E|first3=Campo|last4=J|first4=Menárguez|last5=T|first5=Flores|last6=Pg|first6=Isaacson|date=1998|title=A marginal zone pattern may be found in different varieties of non-Hodgkin's lymphoma: the morphology and immunohistology of splenic involvement by B-cell lymphomas simulating splenic marginal zone lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/9777389/|language=en|pmid=9777389}}</ref>
−*Gastrointestinal
−**May mimic lymphoepithelial lesions in marginal zone lymphoma <ref>{{Cite journal|last=M|first=Fraga|last2=E|first2=Lloret|last3=L|first3=Sanchez-Verde|last4=Jl|first4=Orradre|last5=E|first5=Campo|last6=F|first6=Bosch|last7=Ma|first7=Piris|date=1995|title=Mucosal mantle cell (centrocytic) lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/7657310/|language=en|pmid=7657310}}</ref>
−*Relapse
−**Loss of a mantle zone growth pattern
−**Increase in nuclear size
−**Pleomorphism and chromatin dispersal
−**Increase in mitotic activity and Ki67
−**Cases that are blastoid at diagnosis may relapse with classic morphology <ref>{{Cite journal|last=N|first=Vogt|last2=W|first2=Klapper|date=2013|title=Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression|url=https://pubmed.ncbi.nlm.nih.gov/23240716/|language=en|pmid=23240716}}</ref>
−==Immunophenotype==
+
+|CD43+|-
−|Positive
−|IgM+/- IgD
−|-
−|Positive
−|BCL-2
−|-
−|Positive (flow cytometry)
−|FMC-7
−|-
−|Positive (50% in small subset of cells)
−|MUM1 / IRF4
−|-
−|Positive (subset)
−|MYC
−|-
−|Positive (subset)
−|p53
−|-
−|Positive/ Negative
−|CD10
−|-
−|Positive/ Negative
−|BCL-6
−|-
−|Negative
−|T-cell associated markers (except CD5)
−|-
−|Negative
−|CD200
−|-
−|Negative
−|LEF-1
−|}
−
−*Ki67 count <ref>{{Cite journal|last=W|first=Klapper|last2=E|first2=Hoster|last3=O|first3=Determann|last4=I|first4=Oschlies|last5=J|first5=van der Laak|last6=F|first6=Berger|last7=Hw|first7=Bernd|last8=J|first8=Cabeçadas|last9=E|first9=Campo|date=2009|title=Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network|url=https://pubmed.ncbi.nlm.nih.gov/19669190/|language=en|doi=10.1007/s12308-009-0036-x|pmc=PMC2725281|pmid=19669190}}</ref>
−**Five independent high power fields count
−**Avoidance of residual germinal centers, hot spots and proliferating T cells
−**Note: Ki67 index is not sufficient to classify as blastoid or pleomorphic subtype
−**Classical mantle cell lymphoma might also show high cell proliferation<ref>{{Cite journal|last=O|first=Determann|last2=E|first2=Hoster|last3=G|first3=Ott|last4=H|first4=Wolfram Bernd|last5=C|first5=Loddenkemper|last6=M|first6=Leo Hansmann|last7=Te|first7=Barth|last8=M|first8=Unterhalt|last9=W|first9=Hiddemann|date=2008|title=Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group|url=https://pubmed.ncbi.nlm.nih.gov/18077791/|language=en|pmid=18077791}}</ref>
−*p53 in subset; intense expression correlates with ''TP53'' gene mutation
−**Note: no protein expression; on the other hand, cannot predict the homozygous deletions of the locus <ref>{{Cite journal|last=L|first=Hernandez|last2=T|first2=Fest|last3=M|first3=Cazorla|last4=J|first4=Teruya-Feldstein|last5=F|first5=Bosch|last6=Ma|first6=Peinado|last7=Ma|first7=Piris|last8=E|first8=Montserrat|last9=A|first9=Cardesa|date=1996|title=p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/8605352/|language=en|pmid=8605352}}</ref>
−*MYC in subset
−**High expression correlates with ''MYC'' translocation <ref>{{Cite journal|last=Jy|first=Choe|last2=Jy|first2=Yun|last3=Hy|first3=Na|last4=J|first4=Huh|last5=Sj|first5=Shin|last6=Hj|first6=Kim|last7=Jh|first7=Paik|last8=Ya|first8=Kim|last9=Sj|first9=Nam|date=2016|title=MYC overexpression correlates with MYC amplification or translocation, and is associated with poor prognosis in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26100211/|language=en|pmid=26100211}}</ref>
−*CD10+ MCL more associated with diffuse growth pattern, blastoid/pleomorphic morphology, and BCL6 expression<ref>{{Cite journal|last=J|first=Xu|last2=Lj|first2=Medeiros|last3=A|first3=Saksena|last4=M|first4=Wang|last5=J|first5=Zhou|last6=J|first6=Li|last7=Cc|first7=Yin|last8=G|first8=Tang|last9=L|first9=Wang|date=2017|title=CD10-positive mantle cell lymphoma: clinicopathologic and prognostic study of 30 cases|url=https://pubmed.ncbi.nlm.nih.gov/29545910/|language=en|doi=10.18632/oncotarget.23571|pmc=PMC5837746|pmid=29545910}}</ref>
−*CD23: small subset of cases <ref>{{Cite journal|last=S|first=Kumar|last2=Ga|first2=Green|last3=J|first3=Teruya-Feldstein|last4=M|first4=Raffeld|last5=Es|first5=Jaffe|date=1996|title=Use of CD23 (BU38) on paraffin sections in the diagnosis of small lymphocytic lymphoma and mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/8878025/|language=en|pmid=8878025}}</ref>
−*CD200: May be positive in a subset of SOX11 negative mantle cell lymphomas<ref>{{Cite journal|last=B|first=Espinet|last2=A|first2=Ferrer|last3=B|first3=Bellosillo|last4=L|first4=Nonell|last5=A|first5=Salar|last6=C|first6=Fernández-Rodríguez|last7=E|first7=Puigdecanet|last8=J|first8=Gimeno|last9=M|first9=Garcia-Garcia|date=2014|title=Distinction between asymptomatic monoclonal B-cell lymphocytosis with cyclin D1 overexpression and mantle cell lymphoma: from molecular profiling to flow cytometry|url=https://pubmed.ncbi.nlm.nih.gov/24352646/|language=en|doi=10.1158/1078-0432.CCR-13-1077|pmc=PMC4488901|pmid=24352646}}</ref> [[HAEM5:Leukaemic non-nodal mantle cell lymphoma]]
−*LEF-1: positive in 4 - 9% of mantle cell lymphomas <ref>{{Cite journal|last=Dp|first=O'Malley|last2=Jp|first2=Lee|last3=Am|first3=Bellizzi|date=2017|title=Expression of LEF1 in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28038713/|language=en|pmid=28038713}}</ref><ref>{{Cite journal|last=B|first=Sander|last2=L|first2=Quintanilla-Martinez|last3=G|first3=Ott|last4=L|first4=Xerri|last5=I|first5=Kuzu|last6=Jk|first6=Chan|last7=Sh|first7=Swerdlow|last8=E|first8=Campo|date=2016|title=Mantle cell lymphoma--a spectrum from indolent to aggressive disease|url=https://pubmed.ncbi.nlm.nih.gov/26298543/|language=en|pmid=26298543}}</ref>
−*Cyclin D1-negative MCL
−**Morphology, phenotype, gene expression, clinical presentation and evolution similar to cyclin D1-positive MCL <ref>{{Cite journal|last=K|first=Fu|last2=Dd|first2=Weisenburger|last3=Tc|first3=Greiner|last4=S|first4=Dave|last5=G|first5=Wright|last6=A|first6=Rosenwald|last7=M|first7=Chiorazzi|last8=J|first8=Iqbal|last9=S|first9=Gesk|date=2005|title=Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling|url=https://pubmed.ncbi.nlm.nih.gov/16123218/|language=en|doi=10.1182/blood-2005-04-1753|pmc=PMC1895253|pmid=16123218}}</ref>
−**Positive for Sox-11
−**Frequently express cyclin D2 or cyclin D3 (''IG''-mediated translocations) <ref>{{Cite journal|last=I|first=Wlodarska|last2=D|first2=Dierickx|last3=V|first3=Vanhentenrijk|last4=K|first4=Van Roosbroeck|last5=H|first5=Pospísilová|last6=F|first6=Minnei|last7=G|first7=Verhoef|last8=J|first8=Thomas|last9=P|first9=Vandenberghe|date=2008|title=Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/18391076/|language=en|pmid=18391076}}</ref>
−**cyclin E in cases with negative expression of cyclin D and aggressive behavior <ref>{{Cite journal|last=D|first=Martín-Garcia|last2=A|first2=Navarro|last3=R|first3=Valdés-Mas|last4=G|first4=Clot|last5=J|first5=Gutiérrez-Abril|last6=M|first6=Prieto|last7=I|first7=Ribera-Cortada|last8=R|first8=Woroniecka|last9=G|first9=Rymkiewicz|date=2019|title=CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1 - mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30538135/|language=en|doi=10.1182/blood-2018-07-862151|pmc=PMC6396173|pmid=30538135}}</ref>
−==Chromosomal Rearrangements (Gene Fusions)==
−Put your text here and fill in the table+{| class="wikitable sortable"+!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence+!Diagnostic Significance (Yes, No or Unknown)+!Prognostic Significance (Yes, No or Unknown)+!Therapeutic Significance (Yes, No or Unknown)+!Notes+<span class="blue-text">EXAMPLE:</span> 30% (add reference)+ +The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).+
−
−Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span>
+!Prognostic Significance (Yes, No or Unknown)+chr7+|Yes+ +chr8:1-145,138,636 [hg38]+ +chr8+|No+ +Common recurrent secondary finding for t(8;21) (add reference).+
+Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.'')</span>
+See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.'') </span>
+!Therapeutic Significance (Yes, No or Unknown)+!Notes+ +EGFR; Exon 20 mutations+ + +|<span class="blue-text">EXAMPLE:</span> Excludes hairy cell leukemia (HCL) (add reference).+<br />
− +==Genes and Main Pathways Involved==
−Put your text here+
+
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+'''+
{{Under Construction}}
{{Under Construction}}
−<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Mantle Cell Lymphoma]].
+<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Mantle Cell Lymphoma]].
}}</blockquote>
}}</blockquote>
−<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>
+<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>
==Primary Author(s)*==
==Primary Author(s)*==
−* Mahsa Khanlari, MD
+*Mahsa Khanlari, MD
−* Zhenya Tang, MD, PhD
+*Zhenya Tang, MD, PhD
The University Of Texas MD Anderson Cancer Center, Department of Hematopathology, Houston, Texas
The University Of Texas MD Anderson Cancer Center, Department of Hematopathology, Houston, Texas
−==WHO Classification of Disease==
==WHO Classification of Disease==
Line 40:
Line 37:
|}
|}
−==Definition / Description of Disease==
+==WHO Essential and Desirable Genetic Diagnostic Criteria==
−<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
−{| class="wikitable"
−|+
−|WHO Essential Criteria (Genetics)*
−|
−==Synonyms / Terminology==
+|-
−|WHO Desirable Criteria (Genetics)*
−|
−|-
−|Other Classification
−|
−|}
−<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
−==Related Terminology==
−<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
−*2.5%-10% of non-Hodgkin lymphomas <ref>{{Cite journal|last=Ke|first=Smedby|last2=H|first2=Hjalgrim|date=2011|title=Epidemiology and etiology of mantle cell lymphoma and other non-Hodgkin lymphoma subtypes|url=https://pubmed.ncbi.nlm.nih.gov/21945518/|language=en|pmid=21945518}}</ref>
−==Clinical Features==
−{| class="wikitable"
{| class="wikitable"
−|'''Signs and Symptoms'''
+|+
−|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
+|Acceptable
−|
−|-
|-
−|'''Laboratory Findings'''
+|Not Recommended
−|<span class="blue-text">EXAMPLE:</span> Cytopenias
+|
−|}
|}
+==Gene Rearrangements==
−Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
−!Finding!!Marker
+!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
+!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
+!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
+!Established Clinical Significance Per Guidelines - Yes or No (Source)
+!Clinical Relevance Details/Other Notes
|-
|-
−|Positive (>95%)||cyclin D1
+|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
+|<span class="blue-text">EXAMPLE:</span> Common (CML)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
+|<span class="blue-text">EXAMPLE:</span>
+The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
|-
|-
−|Positive (>90%)||Sox-11
+|<span class="blue-text">EXAMPLE:</span> ''CIC''
−|-
+|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
−|Positive (100%)||B-cell associated markers (CD19, CD20, CD22, CD79a/b)
+|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
−|-
+|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
−|Positive (>95%)||CD5
+|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
+|<span class="blue-text">EXAMPLE:</span> D
+|
+|<span class="blue-text">EXAMPLE:</span>
+''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|-
−|Positive
+|<span class="blue-text">EXAMPLE:</span> ''ALK''
−|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
−Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
+|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
+|<span class="blue-text">EXAMPLE:</span> N/A
+|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
+|<span class="blue-text">EXAMPLE:</span> T
+|
+|<span class="blue-text">EXAMPLE:</span>
−Both balanced and unbalanced forms are observed by FISH (add references).
|-
|-
−|<span class="blue-text">EXAMPLE:</span> ''ABL1''
−|<span class="blue-text">EXAMPLE:</span> N/A
−|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
−|<span class="blue-text">EXAMPLE:</span> N/A
−|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
+|<span class="blue-text">EXAMPLE:</span> D, P, T
+|
+|
|-
|-
−|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
+|
−|
−|Yes
+|
−|No
+|
−|Yes
+|
−|<span class="blue-text">EXAMPLE:</span>
+|
−|
−|
−|}
+|}
−<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
+<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
Line 293:
Line 155:
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref>{{Cite journal|last=Martín-Garcia|first=David|last2=Navarro|first2=Alba|last3=Valdés-Mas|first3=Rafael|last4=Clot|first4=Guillem|last5=Gutiérrez-Abril|first5=Jesús|last6=Prieto|first6=Miriam|last7=Ribera-Cortada|first7=Inmaculada|last8=Woroniecka|first8=Renata|last9=Rymkiewicz|first9=Grzegorz|date=02 28, 2019|title=CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1- mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30538135|journal=Blood|volume=133|issue=9|pages=940–951|doi=10.1182/blood-2018-07-862151|issn=1528-0020|pmc=6396173|pmid=30538135}}</ref></blockquote>
+<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}</blockquote><ref>{{Cite journal|last=Martín-Garcia|first=David|last2=Navarro|first2=Alba|last3=Valdés-Mas|first3=Rafael|last4=Clot|first4=Guillem|last5=Gutiérrez-Abril|first5=Jesús|last6=Prieto|first6=Miriam|last7=Ribera-Cortada|first7=Inmaculada|last8=Woroniecka|first8=Renata|last9=Rymkiewicz|first9=Grzegorz|date=02 28, 2019|title=CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1- mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30538135|journal=Blood|volume=133|issue=9|pages=940–951|doi=10.1182/blood-2018-07-862151|issn=1528-0020|pmc=6396173|pmid=30538135}}</ref><blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+</blockquote>
</blockquote>
</blockquote>
−<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
+<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Characteristic Chromosomal Patterns
−* Gene Mutations (SNV/INDEL)}}
+* Gene Mutations (SNV/INDEL)}}</blockquote>
−* Median survival: 5 - 7 years
+*Median survival: 5 - 7 years
−** Mantle cell lymphoma international prognostic index (clinical), MIPI <ref>{{Cite journal|last=E|first=Hoster|last2=M|first2=Dreyling|last3=W|first3=Klapper|last4=C|first4=Gisselbrecht|last5=A|first5=van Hoof|last6=Hc|first6=Kluin-Nelemans|last7=M|first7=Pfreundschuh|last8=M|first8=Reiser|last9=B|first9=Metzner|date=2008|title=A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/17962512/|language=en|pmid=17962512}}</ref>
+**Mantle cell lymphoma international prognostic index (clinical), MIPI <ref>{{Cite journal|last=E|first=Hoster|last2=M|first2=Dreyling|last3=W|first3=Klapper|last4=C|first4=Gisselbrecht|last5=A|first5=van Hoof|last6=Hc|first6=Kluin-Nelemans|last7=M|first7=Pfreundschuh|last8=M|first8=Reiser|last9=B|first9=Metzner|date=2008|title=A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/17962512/|language=en|pmid=17962512}}</ref>
−** Age, performance status, lactate dehydrogenase, leukocyte count
+**Age, performance status, lactate dehydrogenase, leukocyte count
−** 3 morphologic groups with significantly different prognoses
+**3 morphologic groups with significantly different prognoses
−* Adverse outcome (histopathology / molecular)
+*Adverse outcome (histopathology / molecular)
−** High mitotic rate (> 50/mm<sup>2</sup>) <ref>{{Cite journal|last=M|first=Tiemann|last2=C|first2=Schrader|last3=W|first3=Klapper|last4=Mh|first4=Dreyling|last5=E|first5=Campo|last6=A|first6=Norton|last7=F|first7=Berger|last8=P|first8=Kluin|last9=G|first9=Ott|date=2005|title=Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network|url=https://pubmed.ncbi.nlm.nih.gov/16173960/|language=en|pmid=16173960}}</ref>
+**High mitotic rate (> 50/mm<sup>2</sup>) <ref>{{Cite journal|last=M|first=Tiemann|last2=C|first2=Schrader|last3=W|first3=Klapper|last4=Mh|first4=Dreyling|last5=E|first5=Campo|last6=A|first6=Norton|last7=F|first7=Berger|last8=P|first8=Kluin|last9=G|first9=Ott|date=2005|title=Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network|url=https://pubmed.ncbi.nlm.nih.gov/16173960/|language=en|pmid=16173960}}</ref>
−** Ki67 or MIB1 IHC stains (> 30%) <ref>{{Cite journal|last=N|first=Vogt|last2=W|first2=Klapper|date=2013|title=Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression|url=https://pubmed.ncbi.nlm.nih.gov/23240716/|language=en|pmid=23240716}}</ref>
+**Ki67 or MIB1 IHC stains (> 30%) <ref>{{Cite journal|last=N|first=Vogt|last2=W|first2=Klapper|date=2013|title=Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression|url=https://pubmed.ncbi.nlm.nih.gov/23240716/|language=en|pmid=23240716}}</ref>
−** Blastoid and pleomorphic variants <ref>{{Cite journal|last=E|first=Hoster|last2=A|first2=Rosenwald|last3=F|first3=Berger|last4=Hw|first4=Bernd|last5=S|first5=Hartmann|last6=C|first6=Loddenkemper|last7=Tf|first7=Barth|last8=N|first8=Brousse|last9=S|first9=Pileri|date=2016|title=Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network|url=https://pubmed.ncbi.nlm.nih.gov/26926679/|language=en|pmid=26926679}}</ref>
+**Blastoid and pleomorphic variants <ref>{{Cite journal|last=E|first=Hoster|last2=A|first2=Rosenwald|last3=F|first3=Berger|last4=Hw|first4=Bernd|last5=S|first5=Hartmann|last6=C|first6=Loddenkemper|last7=Tf|first7=Barth|last8=N|first8=Brousse|last9=S|first9=Pileri|date=2016|title=Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network|url=https://pubmed.ncbi.nlm.nih.gov/26926679/|language=en|pmid=26926679}}</ref>
−** ''MYC'' rearrangement <ref>{{Cite journal|last=Z|first=Hu|last2=Lj|first2=Medeiros|last3=Z|first3=Chen|last4=W|first4=Chen|last5=S|first5=Li|last6=Sn|first6=Konoplev|last7=X|first7=Lu|last8=Lv|first8=Pham|last9=Kh|first9=Young|date=2017|title=Mantle Cell Lymphoma With MYC Rearrangement: A Report of 17 Patients|url=https://pubmed.ncbi.nlm.nih.gov/27776009/|language=en|pmid=27776009}}</ref><ref name=":0" />
+**''MYC'' rearrangement <ref>{{Cite journal|last=Z|first=Hu|last2=Lj|first2=Medeiros|last3=Z|first3=Chen|last4=W|first4=Chen|last5=S|first5=Li|last6=Sn|first6=Konoplev|last7=X|first7=Lu|last8=Lv|first8=Pham|last9=Kh|first9=Young|date=2017|title=Mantle Cell Lymphoma With MYC Rearrangement: A Report of 17 Patients|url=https://pubmed.ncbi.nlm.nih.gov/27776009/|language=en|pmid=27776009}}</ref><ref name=":0" />
−** ''TP53'' mutation / overexpression / loss (17p) <ref name=":1">{{Cite journal|last=Mh|first=Delfau-Larue|last2=W|first2=Klapper|last3=F|first3=Berger|last4=F|first4=Jardin|last5=J|first5=Briere|last6=G|first6=Salles|last7=O|first7=Casasnovas|last8=P|first8=Feugier|last9=C|first9=Haioun|date=2015|title=High-dose cytarabine does not overcome the adverse prognostic value of CDKN2A and TP53 deletions in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26022239/|language=en|pmid=26022239}}</ref>
+**''TP53'' mutation / overexpression / loss (17p) <ref name=":1">{{Cite journal|last=Mh|first=Delfau-Larue|last2=W|first2=Klapper|last3=F|first3=Berger|last4=F|first4=Jardin|last5=J|first5=Briere|last6=G|first6=Salles|last7=O|first7=Casasnovas|last8=P|first8=Feugier|last9=C|first9=Haioun|date=2015|title=High-dose cytarabine does not overcome the adverse prognostic value of CDKN2A and TP53 deletions in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26022239/|language=en|pmid=26022239}}</ref>
−** Either ''TP53'' mutations or deletions or both associates with poor prognosis<ref name=":2">{{Cite journal|last=S|first=Ferrero|last2=D|first2=Rossi|last3=A|first3=Rinaldi|last4=A|first4=Bruscaggin|last5=V|first5=Spina|last6=Cw|first6=Eskelund|last7=A|first7=Evangelista|last8=R|first8=Moia|last9=I|first9=Kwee|date=2020|title=KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study|url=https://pubmed.ncbi.nlm.nih.gov/31537689/|language=en|doi=10.3324/haematol.2018.214056|pmc=PMC7271566|pmid=31537689}}</ref>
+**Either ''TP53'' mutations or deletions or both associates with poor prognosis<ref name=":2">{{Cite journal|last=S|first=Ferrero|last2=D|first2=Rossi|last3=A|first3=Rinaldi|last4=A|first4=Bruscaggin|last5=V|first5=Spina|last6=Cw|first6=Eskelund|last7=A|first7=Evangelista|last8=R|first8=Moia|last9=I|first9=Kwee|date=2020|title=KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study|url=https://pubmed.ncbi.nlm.nih.gov/31537689/|language=en|doi=10.3324/haematol.2018.214056|pmc=PMC7271566|pmid=31537689}}</ref>
−*** Elevated Ki-67
+***Elevated Ki-67
−*** Higher MIPI-c classes
+***Higher MIPI-c classes
−*** Blastoid morphology
+***Blastoid morphology
−*** Impact on survival independent of these risk factors
+***Impact on survival independent of these risk factors
−*** Higher levels of MRD positivity after allo-stem cell transplant
+***Higher levels of MRD positivity after allo-stem cell transplant
−** ''CDKN2A'' deletion (9p) <ref name=":1" />
+**''CDKN2A'' deletion (9p) <ref name=":1" />
−** Gains in 3q, deletions of 9q <ref>{{Cite journal|last=I|first=Salaverria|last2=A|first2=Zettl|last3=S|first3=Beà|last4=V|first4=Moreno|last5=J|first5=Valls|last6=E|first6=Hartmann|last7=G|first7=Ott|last8=G|first8=Wright|last9=A|first9=Lopez-Guillermo|date=2007|title=Specific secondary genetic alterations in mantle cell lymphoma provide prognostic information independent of the gene expression-based proliferation signature|url=https://pubmed.ncbi.nlm.nih.gov/17296973/|language=en|doi=10.1200/JCO.2006.08.4251|pmc=PMC2366164|pmid=17296973}}</ref>
+**Gains in 3q, deletions of 9q <ref>{{Cite journal|last=I|first=Salaverria|last2=A|first2=Zettl|last3=S|first3=Beà|last4=V|first4=Moreno|last5=J|first5=Valls|last6=E|first6=Hartmann|last7=G|first7=Ott|last8=G|first8=Wright|last9=A|first9=Lopez-Guillermo|date=2007|title=Specific secondary genetic alterations in mantle cell lymphoma provide prognostic information independent of the gene expression-based proliferation signature|url=https://pubmed.ncbi.nlm.nih.gov/17296973/|language=en|doi=10.1200/JCO.2006.08.4251|pmc=PMC2366164|pmid=17296973}}</ref>
−** Patients with ''KMT2D'' mutation <ref name=":2" />
+**Patients with ''KMT2D'' mutation <ref name=":2" />
−*** Chemo-immunotherapy failure
+***Chemo-immunotherapy failure
−*** High-risk patients based on MIPI-C
+***High-risk patients based on MIPI-C
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
</blockquote>
</blockquote>
−==Individual Region Genomic Gain / Loss / LOH==
+==Individual Region Genomic Gain/Loss/LOH==
−Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
−!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
+!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
−!Diagnostic Significance (Yes, No or Unknown)
+!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
−!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
−!Therapeutic Significance (Yes, No or Unknown)
+!'''Clinical Relevance Details/Other Notes'''
−!Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
−7
7
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
−chr7
−chr7:1- 159,335,973 [hg38]
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
−Unknown
−|<span class="blue-text">EXAMPLE:</span> D, P
−|<span class="blue-text">EXAMPLE:</span> No
−|Yes
−|No
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
−Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
−Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
−8
8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
−chr8
−|<span class="blue-text">EXAMPLE:</span>
+Unknown
+|<span class="blue-text">EXAMPLE:</span> D, P
+|
+|<span class="blue-text">EXAMPLE:</span>
+Common recurrent secondary finding for t(8;21) (add references).
+|-
+|<span class="blue-text">EXAMPLE:</span>
+17
+|<span class="blue-text">EXAMPLE:</span> Amp
+|<span class="blue-text">EXAMPLE:</span>
+17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
−''ERBB2''
−|<span class="blue-text">EXAMPLE:</span> D, P, T
−|
−|No
−|No
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
−Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
−|-
+|
+|
+|
+|
+|
+|
+|
|}
|}
−<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
+<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
Secondary chromosomal aberrations<ref>{{Cite journal|last=C|first=Royo|last2=I|first2=Salaverria|last3=Em|first3=Hartmann|last4=A|first4=Rosenwald|last5=E|first5=Campo|last6=S|first6=Beà|date=2011|title=The complex landscape of genetic alterations in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21945515/|language=en|pmid=21945515}}</ref>
Secondary chromosomal aberrations<ref>{{Cite journal|last=C|first=Royo|last2=I|first2=Salaverria|last3=Em|first3=Hartmann|last4=A|first4=Rosenwald|last5=E|first5=Campo|last6=S|first6=Beà|date=2011|title=The complex landscape of genetic alterations in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21945515/|language=en|pmid=21945515}}</ref>
Line 535:
Line 415:
|}
|}
<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
</blockquote>
</blockquote>
−==Characteristic Chromosomal Patterns==
+==Characteristic Chromosomal or Other Global Mutational Patterns==
−Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Chromosomal Pattern
−!Diagnostic Significance (Yes, No or Unknown)
+!Molecular Pathogenesis
−!Prognostic Significance (Yes, No or Unknown)
+!'''Prevalence -'''
−!Therapeutic Significance (Yes, No or Unknown)
+'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
−!Notes
+!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
+!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
+!'''Clinical Relevance Details/Other Notes'''
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
−Co-deletion of 1p and 18q
Co-deletion of 1p and 18q
−|Yes
+|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
−|No
+|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
−|No
+|<span class="blue-text">EXAMPLE:</span> D, P
+|
+|
+|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
−Microsatellite instability - hypermutated
−|
+|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
+|<span class="blue-text">EXAMPLE:</span> P, T
+|
+|
+|-
+|
+|
+|
+|
+|
+|
|}
|}
−<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
+<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>
*''CCND1'' rearrangement; t(11;14)(q13;q32)
*''CCND1'' rearrangement; t(11;14)(q13;q32)
Line 567:
Line 465:
*Cyclin D2 (''CCND2'') rearrangements by FISH in 55%-70% of cyclin D1-negative cases
*Cyclin D2 (''CCND2'') rearrangements by FISH in 55%-70% of cyclin D1-negative cases
*Almost all cyclin D1-negative mantle cell lymphomas carry ''CCND2/CCND3'' rearrangements with immunoglobulin genes (including a novel IGK/L enhancer hijacking mechanism)
*Almost all cyclin D1-negative mantle cell lymphomas carry ''CCND2/CCND3'' rearrangements with immunoglobulin genes (including a novel IGK/L enhancer hijacking mechanism)
−*A broad spectrum of secondary chromosomal aberrations have been reported, especially in MCL with bone marrow and peripheral blood involvement<ref>{{Cite journal|last=Royo|first=Cristina|last2=Salaverria|first2=Itziar|last3=Hartmann|first3=Elena M.|last4=Rosenwald|first4=Andreas|last5=Campo|first5=Elías|last6=Beà|first6=Sílvia|date=2011-11|title=The complex landscape of genetic alterations in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21945515|journal=Seminars in Cancer Biology|volume=21|issue=5|pages=322–334|doi=10.1016/j.semcancer.2011.09.007|issn=1096-3650|pmid=21945515}}</ref>.
+*A broad spectrum of secondary chromosomal aberrations have been reported, especially in MCL with bone marrow and peripheral blood involvement<ref>{{Cite journal|last=Royo|first=Cristina|last2=Salaverria|first2=Itziar|last3=Hartmann|first3=Elena M.|last4=Rosenwald|first4=Andreas|last5=Campo|first5=Elías|last6=Beà|first6=Sílvia|date=2011-11|title=The complex landscape of genetic alterations in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21945515|journal=Seminars in Cancer Biology|volume=21|issue=5|pages=322–334|doi=10.1016/j.semcancer.2011.09.007|issn=1096-3650|pmid=21945515}}</ref>.
*Tetraploidy is more frequent in pleomorphic (80%) and blastoid (36%) variants than in classic MCLs (8%) <ref>{{Cite journal|last=G|first=Ott|last2=J|first2=Kalla|last3=Mm|first3=Ott|last4=B|first4=Schryen|last5=T|first5=Katzenberger|last6=Jg|first6=Müller|last7=Hk|first7=Müller-Hermelink|date=1997|title=Blastoid variants of mantle cell lymphoma: frequent bcl-1 rearrangements at the major translocation cluster region and tetraploid chromosome clones|url=https://pubmed.ncbi.nlm.nih.gov/9028966/|language=en|pmid=9028966}}</ref>
*Tetraploidy is more frequent in pleomorphic (80%) and blastoid (36%) variants than in classic MCLs (8%) <ref>{{Cite journal|last=G|first=Ott|last2=J|first2=Kalla|last3=Mm|first3=Ott|last4=B|first4=Schryen|last5=T|first5=Katzenberger|last6=Jg|first6=Müller|last7=Hk|first7=Müller-Hermelink|date=1997|title=Blastoid variants of mantle cell lymphoma: frequent bcl-1 rearrangements at the major translocation cluster region and tetraploid chromosome clones|url=https://pubmed.ncbi.nlm.nih.gov/9028966/|language=en|pmid=9028966}}</ref>
*t(8;14)(q24;q32)/MYC-IGH in small subset of cases <ref name=":0">{{Cite journal|last=L|first=Wang|last2=G|first2=Tang|last3=Lj|first3=Medeiros|last4=J|first4=Xu|last5=W|first5=Huang|last6=Cc|first6=Yin|last7=M|first7=Wang|last8=P|first8=Jain|last9=P|first9=Lin|date=2020|title=MYC rearrangement but not extra MYC copies is an independent prognostic factor in patients with mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/32273477/|language=en|pmid=32273477}}</ref><ref>{{Cite journal|last=Un|first=Vaishampayan|last2=An|first2=Mohamed|last3=Mc|first3=Dugan|last4=Re|first4=Bloom|last5=M|first5=Palutke|date=2001|title=Blastic mantle cell lymphoma associated with Burkitt-type translocation and hypodiploidy|url=https://pubmed.ncbi.nlm.nih.gov/11722412/|language=en|pmid=11722412}}</ref>
*t(8;14)(q24;q32)/MYC-IGH in small subset of cases <ref name=":0">{{Cite journal|last=L|first=Wang|last2=G|first2=Tang|last3=Lj|first3=Medeiros|last4=J|first4=Xu|last5=W|first5=Huang|last6=Cc|first6=Yin|last7=M|first7=Wang|last8=P|first8=Jain|last9=P|first9=Lin|date=2020|title=MYC rearrangement but not extra MYC copies is an independent prognostic factor in patients with mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/32273477/|language=en|pmid=32273477}}</ref><ref>{{Cite journal|last=Un|first=Vaishampayan|last2=An|first2=Mohamed|last3=Mc|first3=Dugan|last4=Re|first4=Bloom|last5=M|first5=Palutke|date=2001|title=Blastic mantle cell lymphoma associated with Burkitt-type translocation and hypodiploidy|url=https://pubmed.ncbi.nlm.nih.gov/11722412/|language=en|pmid=11722412}}</ref>
+
{| class="wikitable"
{| class="wikitable"
−|Parameter
+|Parameter
|n
|n
|%
|%
|-
|-
−!'''''CCND2'' translocation'''
+!'''''CCND2'' translocation'''
!
!
!
!
Line 591:
Line 490:
!'''13'''
!'''13'''
|-
|-
−! '''CCND2-break'''
+!'''CCND2-break'''
!2/40
!2/40
!'''5'''
!'''5'''
|-
|-
−| '''CCDND2-?'''
+|'''CCDND2-?'''
|'''2/40'''
|'''2/40'''
|'''5'''
|'''5'''
|-
|-
−| '''Negative'''
+|'''Negative'''
|'''18/40'''
|'''18/40'''
|'''45'''
|'''45'''
|}
|}
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
</blockquote>
</blockquote>
−==Gene Mutations (SNV / INDEL)==
+==Gene Mutations (SNV/INDEL)==
−Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
−!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC / TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
+!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
−!'''Diagnostic Significance (Yes, No or Unknown)'''
+'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
−!Prognostic Significance (Yes, No or Unknown)
+!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T '''
−!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
−!'''Clinical Relevance Details/Other Notes'''
|-
|-
−|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
+|<span class="blue-text">EXAMPLE:</span>''EGFR''
−<span class="blue-text">EXAMPLE:</span>
+<br />
−|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
−|<span class="blue-text">EXAMPLE:</span> Oncogene
−|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
−<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> T
−|<span class="blue-text">EXAMPLE:</span> TSG
+|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
−|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
+|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
−|-
−<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
+|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
−|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
+<br />
−|<span class="blue-text">EXAMPLE:</span> EGFR amplification
+|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
+|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
+|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
+|<span class="blue-text">EXAMPLE:</span> P
+|
+|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
+|-
+|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> Activating mutations
+|<span class="blue-text">EXAMPLE:</span> Oncogene
+|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
+|<span class="blue-text">EXAMPLE:</span> T
+|
+|
+|-
+|
+|
+|
+|
|
|
|
|
|
|
−|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
−|}
−Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
−<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>
−<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
Line 654:
Line 570:
|-
|-
|CARD11
|CARD11
−|B-cell receptor signaling
+|B-cell receptor signaling
|8.5-16.3%
|8.5-16.3%
|-
|-
Line 662:
Line 578:
|-
|-
|BTK
|BTK
−|B-cell receptor signaling
+|B-cell receptor signaling
|5.5-17.1%
|5.5-17.1%
|-
|-
Line 670:
Line 586:
|-
|-
|CCND1
|CCND1
−|CDK kinase regulator
+|CDK kinase regulator
|20.2-27.7%
|20.2-27.7%
|-
|-
Line 678:
Line 594:
|-
|-
|SMARCA4
|SMARCA4
−|Chromatin modification
+|Chromatin modification
|14.9-18.7%
|14.9-18.7%
|-
|-
Line 694:
Line 610:
|-
|-
|ATM
|ATM
−|DNA damage response
+|DNA damage response
|43.5-57.6%
|43.5-57.6%
|-
|-
|KMT2D
|KMT2D
−|Histone modification
+|Histone modification
|18.4-21.8%
|18.4-21.8%
|-
|-
Line 718:
Line 634:
|-
|-
|IGH
|IGH
−|Immune response
+|Immune response
|21.5-38.4%
|21.5-38.4%
|-
|-
Line 738:
Line 654:
|-
|-
|TET2
|TET2
−|Myelopoiesis
+|Myelopoiesis
|5.6-14.1%
|5.6-14.1%
|-
|-
|NOTCH1
|NOTCH1
−|NOTCH signaling pathway
+|NOTCH signaling pathway
|10.8-14.8%
|10.8-14.8%
|-
|-
Line 750:
Line 666:
|-
|-
|UBR5
|UBR5
−|Protein ligases
+|Protein ligases
|17.8%
|17.8%
|-
|-
|TP53
|TP53
−|Tumor suppressor
+|Tumor suppressor
|26.8-43.0%
|26.8-43.0%
|-
|-
Line 763:
Line 679:
−<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref>{{Cite journal|last=Rosenquist|first=R.|last2=Beà|first2=S.|last3=Du|first3=M.-Q.|last4=Nadel|first4=B.|last5=Pan-Hammarström|first5=Q.|date=11 2017|title=Genetic landscape and deregulated pathways in B-cell lymphoid malignancies|url=https://pubmed.ncbi.nlm.nih.gov/28631441|journal=Journal of Internal Medicine|volume=282|issue=5|pages=371–394|doi=10.1111/joim.12633|issn=1365-2796|pmid=28631441}}</ref></blockquote>
+<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}</blockquote><ref>{{Cite journal|last=Rosenquist|first=R.|last2=Beà|first2=S.|last3=Du|first3=M.-Q.|last4=Nadel|first4=B.|last5=Pan-Hammarström|first5=Q.|date=11 2017|title=Genetic landscape and deregulated pathways in B-cell lymphoid malignancies|url=https://pubmed.ncbi.nlm.nih.gov/28631441|journal=Journal of Internal Medicine|volume=282|issue=5|pages=371–394|doi=10.1111/joim.12633|issn=1365-2796|pmid=28631441}}</ref><blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
+</blockquote>
</blockquote>
</blockquote>
==Epigenomic Alterations==
==Epigenomic Alterations==
+
Put your text here
Put your text here
+==Genes and Main Pathways Involved==
−Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
+Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
−|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
+|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|-
|-
−|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
+|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|-
−|<span class="blue-text">EXAMPLE:</span> KMT2C and ARID1A; Inactivating mutations
+|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
−|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
+|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
−|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
+|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
+|-
+|
+|
+|
|}
|}
−<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
+<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>
Please refer to Gene Mutations (SNV/INDEL)
Please refer to Gene Mutations (SNV/INDEL)
+<blockquote class="blockedit">
+<center><span style="color:Maroon">'''End of V4 Section'''</span>
+----
</blockquote>
</blockquote>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
−* Tissue biopsy (lymph node / extranodal sites): monomorphic proliferation of small to intermediate sized B cells with overexpression of cyclin D1 or SOX11
+*Tissue biopsy (lymph node / extranodal sites): monomorphic proliferation of small to intermediate sized B cells with overexpression of cyclin D1 or SOX11
−* t(11;14)(q13;q32) ''IGH/CCND1''
+*t(11;14)(q13;q32) ''IGH/CCND1''
−* MRD is defined as the minimal traceable persistence of lymphoma cells after a successful treatment.
+*MRD is defined as the minimal traceable persistence of lymphoma cells after a successful treatment.
−* Many methods to monitor MRD have been published
+*Many methods to monitor MRD have been published
−* The most sensitive and the most commonly used and best standardized approach in MCL: allele-specific oligonucleotide (ASO) quantitative polymerase chain reaction (qPCR) method <ref>{{Cite journal|last=Ferrero|first=Simone|last2=Dreyling|first2=Martin|last3=European Mantle Cell Lymphoma Network|date=07 2017|title=Minimal residual disease in mantle cell lymphoma: are we ready for a personalized treatment approach?|url=https://pubmed.ncbi.nlm.nih.gov/28655809|journal=Haematologica|volume=102|issue=7|pages=1133–1136|doi=10.3324/haematol.2017.167627|issn=1592-8721|pmc=5566011|pmid=28655809}}</ref>
+*The most sensitive and the most commonly used and best standardized approach in MCL: allele-specific oligonucleotide (ASO) quantitative polymerase chain reaction (qPCR) method <ref>{{Cite journal|last=Ferrero|first=Simone|last2=Dreyling|first2=Martin|last3=European Mantle Cell Lymphoma Network|date=07 2017|title=Minimal residual disease in mantle cell lymphoma: are we ready for a personalized treatment approach?|url=https://pubmed.ncbi.nlm.nih.gov/28655809|journal=Haematologica|volume=102|issue=7|pages=1133–1136|doi=10.3324/haematol.2017.167627|issn=1592-8721|pmc=5566011|pmid=28655809}}</ref>
==Familial Forms==
==Familial Forms==
−* Family history of leukemia may elevate risks particularly among men with mantle-cell lymphomas (OR = 3.1, 95% CI = 1.6-6.2)<ref>{{Cite journal|last=Ss|first=Wang|last2=Sl|first2=Slager|last3=P|first3=Brennan|last4=Ea|first4=Holly|last5=S|first5=De Sanjose|last6=L|first6=Bernstein|last7=P|first7=Boffetta|last8=Jr|first8=Cerhan|last9=M|first9=Maynadie|date=2007|title=Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph)|url=https://pubmed.ncbi.nlm.nih.gov/17185468/|language=en|doi=10.1182/blood-2006-06-031948|pmc=PMC1852242|pmid=17185468}}</ref>
+*Family history of leukemia may elevate risks particularly among men with mantle-cell lymphomas (OR = 3.1, 95% CI = 1.6-6.2)<ref>{{Cite journal|last=Ss|first=Wang|last2=Sl|first2=Slager|last3=P|first3=Brennan|last4=Ea|first4=Holly|last5=S|first5=De Sanjose|last6=L|first6=Bernstein|last7=P|first7=Boffetta|last8=Jr|first8=Cerhan|last9=M|first9=Maynadie|date=2007|title=Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph)|url=https://pubmed.ncbi.nlm.nih.gov/17185468/|language=en|doi=10.1182/blood-2006-06-031948|pmc=PMC1852242|pmid=17185468}}</ref>
==Additional Information==
==Additional Information==
−This disease is <u>defined/characterized</u> as detailed below:
+*Clinically aggressive, mature B cell lymphoma
+*Small to medium sized lymphoid cells (monomorphic, except in pleomorphic variant)
+*Associated with t(11;14)(q13;q32) and cyclin D1 overexpression in over 95% of cases
+*Synonyms/Terminology - Centrocytic malignant lymphoma (obsolete) <ref name=":3">{{Cite journal|last=K|first=Lennert|last2=H|first2=Stein|last3=E|first3=Kaiserling|date=1975|title=Cytological and functional criteria for the classification of malignant lymphomata|url=https://pubmed.ncbi.nlm.nih.gov/52366/|language=en|pmc=PMC2149614|pmid=52366}}</ref>; Lymphocytic lymphoma of intermediate differentiation <ref name=":4">{{Cite journal|last=H|first=Kim|last2=Rj|first2=Zelman|last3=Ma|first3=Fox|last4=Jm|first4=Bennett|last5=Cw|first5=Berard|last6=Jj|first6=Butler|last7=Ge|first7=Byrne|last8=Rf|first8=Dorfman|last9=Rj|first9=Hartsock|date=1982|title=Pathology Panel for Lymphoma Clinical Studies: a comprehensive analysis of cases accumulated since its inception|url=https://pubmed.ncbi.nlm.nih.gov/6948126/|language=en|pmid=6948126}}</ref>; Mantle zone lymphoma <ref name=":5">{{Cite journal|last=Dd|first=Weisenburger|last2=H|first2=Kim|last3=H|first3=Rappaport|date=1982|title=Mantle-zone lymphoma: a follicular variant of intermediate lymphocytic lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/6895860/|language=en|pmid=6895860}}</ref>; Malignant lymphomatous polyposis; in situ mantle cell lymphoma (for in situ mantle cell neoplasia)
+The <u>epidemiology/prevalence</u> of this disease is detailed below:
+*~ 7% of B cell lymphomas <ref name=":6">{{Cite journal|date=1997|title=A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project|url=https://pubmed.ncbi.nlm.nih.gov/9166827/|language=en|pmid=9166827}}</ref>
+*2.5%-10% of non-Hodgkin lymphomas <ref name=":7">{{Cite journal|last=Ke|first=Smedby|last2=H|first2=Hjalgrim|date=2011|title=Epidemiology and etiology of mantle cell lymphoma and other non-Hodgkin lymphoma subtypes|url=https://pubmed.ncbi.nlm.nih.gov/21945518/|language=en|pmid=21945518}}</ref>
+*Age adjusted incidence: 0.7/100,000 person years in white population in USA <ref name=":8">{{Cite journal|last=B|first=Aschebrook-Kilfoy|last2=Db|first2=Caces|last3=Nj|first3=Ollberding|last4=Sm|first4=Smith|last5=Bc|first5=Chiu|date=2013|title=An upward trend in the age-specific incidence patterns for mantle cell lymphoma in the USA|url=https://pubmed.ncbi.nlm.nih.gov/23350889/|language=en|pmid=23350889}}</ref>
+*Median age: 60 years<ref name=":9">{{Cite journal|last=Lh|first=Argatoff|last2=Jm|first2=Connors|last3=Rj|first3=Klasa|last4=De|first4=Horsman|last5=Rd|first5=Gascoyne|date=1997|title=Mantle cell lymphoma: a clinicopathologic study of 80 cases|url=https://pubmed.ncbi.nlm.nih.gov/9058729/|language=en|pmid=9058729}}</ref>
+*M:F = 3:1 (range, 1.6-6.8 :1)<ref name=":10">{{Cite journal|last=P|first=Lardelli|last2=Ma|first2=Bookman|last3=J|first3=Sundeen|last4=Dl|first4=Longo|last5=Es|first5=Jaffe|date=1990|title=Lymphocytic lymphoma of intermediate differentiation. Morphologic and immunophenotypic spectrum and clinical correlations|url=https://pubmed.ncbi.nlm.nih.gov/2198813/|language=en|pmid=2198813}}</ref>
+The <u>clinical features</u> of this disease<ref>Arber, D.A., et al., ''Hematopathology''. 2017, Philadelphia, PA: Elsevier.</ref> are detailed below:
+*Approximately 70% with stage IV disease at presentation
+**Generalized lymphadenopathy, hepatosplenomegaly and bone marrow involvement
+**40-50% with B symptoms
+**Two subtypes based on clinical presentation:
+***More aggressive, with SOX11 overexpression (SOX11+disease), nodal presentation (the most common subtype)
+***More indolent, without SOX11 expression (SOX11-disease), leukemic presentation, and non-nodal disease
+*Peripheral blood:
+**Atypical lymphoid cells: present virtually in all cases by flow cytometry <ref>{{Cite journal|last=A|first=Ferrer|last2=I|first2=Salaverria|last3=F|first3=Bosch|last4=N|first4=Villamor|last5=M|first5=Rozman|last6=S|first6=Beà|last7=E|first7=Giné|last8=A|first8=López-Guillermo|last9=E|first9=Campo|date=2007|title=Leukemic involvement is a common feature in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/17477385/|language=en|pmid=17477385}}</ref>
+***Atypical lymphoid cells can be detected in the peripheral blood in the absence of lymphocytosis
+***Leukemic involvement: 20 - 70% of patients at diagnosis
+***Leukemic involvement is usually a sign of disease progression
+**Blastoid morphology of the circulating lymphoma cells may mimic acute leukemia
+**A leukemic phase with no or minimal lymph node involvement is possible, [[HAEM5:Leukaemic non-nodal mantle cell lymphoma]]
+***Asymptomatic for long period
+***Splenomegaly
+**Anemia and thrombocytopenia (10%- 40%)
+*Multiple intestinal polyps (lymphomatous polyposis)
+*Progress to blastoid / pleomorphic variant
+**At the time of relapse (~22%)
+The <u>sites of involvement</u> of this disease are detailed below:
+*Lymph node
+*Bone marrow involvement independent of peripheral blood (50 - 90%), peripheral blood (20 - 70%), spleen (~50%), liver (~20%) <ref name=":11">{{Cite journal|last=J|first=Wasman|last2=Ns|first2=Rosenthal|last3=Dc|first3=Farhi|date=1996|title=Mantle cell lymphoma. Morphologic findings in bone marrow involvement|url=https://pubmed.ncbi.nlm.nih.gov/8712173/|language=en|pmid=8712173}}</ref><ref name=":12">{{Cite journal|last=Ma|first=Vasef|last2=Lj|first2=Medeiros|last3=C|first3=Koo|last4=A|first4=McCourty|last5=Rk|first5=Brynes|date=1997|title=Cyclin D1 immunohistochemical staining is useful in distinguishing mantle cell lymphoma from other low-grade B-cell neoplasms in bone marrow|url=https://pubmed.ncbi.nlm.nih.gov/9291459/|language=en|pmid=9291459}}</ref><ref name=":13">{{Cite journal|last=H|first=Samaha|last2=C|first2=Dumontet|last3=N|first3=Ketterer|last4=I|first4=Moullet|last5=C|first5=Thieblemont|last6=F|first6=Bouafia|last7=E|first7=Callet-Bauchu|last8=P|first8=Felman|last9=F|first9=Berger|date=1998|title=Mantle cell lymphoma: a retrospective study of 121 cases|url=https://pubmed.ncbi.nlm.nih.gov/9697885/|language=en|pmid=9697885}}</ref>
+*Frequent extranodal site involvement : gastrointestinal tract, Waldeyer ring, lungs, pleura, skin, CNS
+**CNS involvement may occur mostly at the time of relapse<ref name=":14">{{Cite journal|last=Cy|first=Cheah|last2=A|first2=George|last3=E|first3=Giné|last4=A|first4=Chiappella|last5=Hc|first5=Kluin-Nelemans|last6=W|first6=Jurczak|last7=K|first7=Krawczyk|last8=H|first8=Mocikova|last9=P|first9=Klener|date=2013|title=Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network|url=https://pubmed.ncbi.nlm.nih.gov/23616279/|language=en|pmid=23616279}}</ref>
+*Extranodal involvement without lymphadenopathies: 4 - 15%
+The <u>morphologic features</u> of this disease are detailed below:
+*Architectural pattern: Diffuse > nodular > mantle zone growth patterns
+**Nodal (> 50% nodular), diffuse growth pattern (< 50% nodular)
+*Cytologic variants: Classic, blastoid, pleomorphic, small cell, marginal zone-like
+*Blastoid and pleomorphic cytologic variants are known as aggressive variants of MCL
+*Classic variant:
+**Small to medium monomorphic lymphoid neoplasm
+**Irregular nuclear border, clumped chromatin and inconspicuous nucleoli
+**No proliferation centers
+**No centroblasts, immunoblasts or paraimmunoblasts
+**Hyalinized vessels
+**Epithelioid histiocytes
+**Follicular dendritic cell (FDC) meshwork
+***Nodular pattern
+****Primary follicle-like pattern
+****Germinal center-like pattern
+***Diffuse pattern
+*Aggressive variants
+**Blastoid: lymphoblast-like in appearance, monomorphic
+***>20 - 30 mitoses per 10 high power fields
+***Resemble lymphoblastic lymphoma
+**Pleomorphic: large cells with irregular nuclear border, cerebriform nuclei, multinucleation, lack of monomorphism
+***Prominent nucleoli and abundant pale cytoplasm
+***Resemble DLBCL
+*Other variants
+**Small cell: small round lymphocytes with more clumped chromatin
+***Resemble CLL
+**Marginal zone-like: abundant pale cytoplasm
+***Resembling marginal zone or monocytoid B cells
+**Lymphoplasmacytic differentiation, some cases <ref name=":15">{{Cite journal|last=Kh|first=Young|last2=Wc|first2=Chan|last3=K|first3=Fu|last4=J|first4=Iqbal|last5=Wg|first5=Sanger|last6=A|first6=Ratashak|last7=Tc|first7=Greiner|last8=Dd|first8=Weisenburger|date=2006|title=Mantle cell lymphoma with plasma cell differentiation|url=https://pubmed.ncbi.nlm.nih.gov/16861965/|language=en|pmid=16861965}}</ref>
+*Bone marrow
+**Nodular, interstitial or paratrabecular or combination
+*Peripheral blood (see below)
+**Similar spectrum seen in tissue sample
+**Nucleoli are sometimes more prominent
+*Spleen
+**White pulp nodules involved (enlarged)
+**Variable involvement of the red pulp
+**Residual naked germinal centers
+**Tumor cells: similar monotonous morphology
+**Some cases may show a marginal zone-like area <ref name=":16">{{Cite journal|last=Ma|first=Piris|last2=M|first2=Mollejo|last3=E|first3=Campo|last4=J|first4=Menárguez|last5=T|first5=Flores|last6=Pg|first6=Isaacson|date=1998|title=A marginal zone pattern may be found in different varieties of non-Hodgkin's lymphoma: the morphology and immunohistology of splenic involvement by B-cell lymphomas simulating splenic marginal zone lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/9777389/|language=en|pmid=9777389}}</ref>
+*Gastrointestinal
+**May mimic lymphoepithelial lesions in marginal zone lymphoma <ref name=":17">{{Cite journal|last=M|first=Fraga|last2=E|first2=Lloret|last3=L|first3=Sanchez-Verde|last4=Jl|first4=Orradre|last5=E|first5=Campo|last6=F|first6=Bosch|last7=Ma|first7=Piris|date=1995|title=Mucosal mantle cell (centrocytic) lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/7657310/|language=en|pmid=7657310}}</ref>
+*Relapse
+**Loss of a mantle zone growth pattern
+**Increase in nuclear size
+**Pleomorphism and chromatin dispersal
+**Increase in mitotic activity and Ki67
+**Cases that are blastoid at diagnosis may relapse with classic morphology <ref name=":18">{{Cite journal|last=N|first=Vogt|last2=W|first2=Klapper|date=2013|title=Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression|url=https://pubmed.ncbi.nlm.nih.gov/23240716/|language=en|pmid=23240716}}</ref>
+The <u>immunophenotype</u> of this disease is detailed below:
+*Positive (universal) - Cyclin D1 (>95%), Sox-11 (>90%), B-cell associated markers (CD19, CD20, CD22, CD79a/b) (100%, CD5 (>95%), CD43, IgM+/- IgD, BCL-2, FMC-7 (flow cytometry)
+*Positive (subset) - MUM1 / IRF4 (50% in small subset of cells), MYC, p53
+*Positive/Negative - CD10, BCL-6
+*Negative (universal) - T-cell associated markers (except CD5), CD200, LEF-1
+*Ki67 count <ref name=":19">{{Cite journal|last=W|first=Klapper|last2=E|first2=Hoster|last3=O|first3=Determann|last4=I|first4=Oschlies|last5=J|first5=van der Laak|last6=F|first6=Berger|last7=Hw|first7=Bernd|last8=J|first8=Cabeçadas|last9=E|first9=Campo|date=2009|title=Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network|url=https://pubmed.ncbi.nlm.nih.gov/19669190/|language=en|doi=10.1007/s12308-009-0036-x|pmc=PMC2725281|pmid=19669190}}</ref>
+**Five independent high-power fields count
+**Avoidance of residual germinal centers, hot spots and proliferating T cells
+**Note: Ki67 index is not sufficient to classify as blastoid or pleomorphic subtype
+**Classical mantle cell lymphoma might also show high cell proliferation<ref name=":20">{{Cite journal|last=O|first=Determann|last2=E|first2=Hoster|last3=G|first3=Ott|last4=H|first4=Wolfram Bernd|last5=C|first5=Loddenkemper|last6=M|first6=Leo Hansmann|last7=Te|first7=Barth|last8=M|first8=Unterhalt|last9=W|first9=Hiddemann|date=2008|title=Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group|url=https://pubmed.ncbi.nlm.nih.gov/18077791/|language=en|pmid=18077791}}</ref>
+*p53 in subset; intense expression correlates with ''TP53'' gene mutation
+**Note: no protein expression; on the other hand, cannot predict the homozygous deletions of the locus <ref name=":21">{{Cite journal|last=L|first=Hernandez|last2=T|first2=Fest|last3=M|first3=Cazorla|last4=J|first4=Teruya-Feldstein|last5=F|first5=Bosch|last6=Ma|first6=Peinado|last7=Ma|first7=Piris|last8=E|first8=Montserrat|last9=A|first9=Cardesa|date=1996|title=p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/8605352/|language=en|pmid=8605352}}</ref>
+*MYC in subset
+**High expression correlates with ''MYC'' translocation <ref name=":22">{{Cite journal|last=Jy|first=Choe|last2=Jy|first2=Yun|last3=Hy|first3=Na|last4=J|first4=Huh|last5=Sj|first5=Shin|last6=Hj|first6=Kim|last7=Jh|first7=Paik|last8=Ya|first8=Kim|last9=Sj|first9=Nam|date=2016|title=MYC overexpression correlates with MYC amplification or translocation, and is associated with poor prognosis in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26100211/|language=en|pmid=26100211}}</ref>
+*CD10+ MCL more associated with diffuse growth pattern, blastoid/pleomorphic morphology, and BCL6 expression<ref name=":23">{{Cite journal|last=J|first=Xu|last2=Lj|first2=Medeiros|last3=A|first3=Saksena|last4=M|first4=Wang|last5=J|first5=Zhou|last6=J|first6=Li|last7=Cc|first7=Yin|last8=G|first8=Tang|last9=L|first9=Wang|date=2017|title=CD10-positive mantle cell lymphoma: clinicopathologic and prognostic study of 30 cases|url=https://pubmed.ncbi.nlm.nih.gov/29545910/|language=en|doi=10.18632/oncotarget.23571|pmc=PMC5837746|pmid=29545910}}</ref>
+*CD23: small subset of cases <ref name=":24">{{Cite journal|last=S|first=Kumar|last2=Ga|first2=Green|last3=J|first3=Teruya-Feldstein|last4=M|first4=Raffeld|last5=Es|first5=Jaffe|date=1996|title=Use of CD23 (BU38) on paraffin sections in the diagnosis of small lymphocytic lymphoma and mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/8878025/|language=en|pmid=8878025}}</ref>
+*CD200: May be positive in a subset of SOX11 negative mantle cell lymphomas<ref name=":25">{{Cite journal|last=B|first=Espinet|last2=A|first2=Ferrer|last3=B|first3=Bellosillo|last4=L|first4=Nonell|last5=A|first5=Salar|last6=C|first6=Fernández-Rodríguez|last7=E|first7=Puigdecanet|last8=J|first8=Gimeno|last9=M|first9=Garcia-Garcia|date=2014|title=Distinction between asymptomatic monoclonal B-cell lymphocytosis with cyclin D1 overexpression and mantle cell lymphoma: from molecular profiling to flow cytometry|url=https://pubmed.ncbi.nlm.nih.gov/24352646/|language=en|doi=10.1158/1078-0432.CCR-13-1077|pmc=PMC4488901|pmid=24352646}}</ref> [[HAEM5:Leukaemic non-nodal mantle cell lymphoma]]
+*LEF-1: positive in 4 - 9% of mantle cell lymphomas <ref name=":26">{{Cite journal|last=Dp|first=O'Malley|last2=Jp|first2=Lee|last3=Am|first3=Bellizzi|date=2017|title=Expression of LEF1 in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28038713/|language=en|pmid=28038713}}</ref><ref name=":27">{{Cite journal|last=B|first=Sander|last2=L|first2=Quintanilla-Martinez|last3=G|first3=Ott|last4=L|first4=Xerri|last5=I|first5=Kuzu|last6=Jk|first6=Chan|last7=Sh|first7=Swerdlow|last8=E|first8=Campo|date=2016|title=Mantle cell lymphoma--a spectrum from indolent to aggressive disease|url=https://pubmed.ncbi.nlm.nih.gov/26298543/|language=en|pmid=26298543}}</ref>
+*Cyclin D1-negative MCL
+**Morphology, phenotype, gene expression, clinical presentation and evolution similar to cyclin D1-positive MCL <ref name=":28">{{Cite journal|last=K|first=Fu|last2=Dd|first2=Weisenburger|last3=Tc|first3=Greiner|last4=S|first4=Dave|last5=G|first5=Wright|last6=A|first6=Rosenwald|last7=M|first7=Chiorazzi|last8=J|first8=Iqbal|last9=S|first9=Gesk|date=2005|title=Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling|url=https://pubmed.ncbi.nlm.nih.gov/16123218/|language=en|doi=10.1182/blood-2005-04-1753|pmc=PMC1895253|pmid=16123218}}</ref>
+**Positive for Sox-11
+**Frequently express cyclin D2 or cyclin D3 (''IG''-mediated translocations) <ref name=":29">{{Cite journal|last=I|first=Wlodarska|last2=D|first2=Dierickx|last3=V|first3=Vanhentenrijk|last4=K|first4=Van Roosbroeck|last5=H|first5=Pospísilová|last6=F|first6=Minnei|last7=G|first7=Verhoef|last8=J|first8=Thomas|last9=P|first9=Vandenberghe|date=2008|title=Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/18391076/|language=en|pmid=18391076}}</ref>
+**cyclin E in cases with negative expression of cyclin D and aggressive behavior <ref name=":30">{{Cite journal|last=D|first=Martín-Garcia|last2=A|first2=Navarro|last3=R|first3=Valdés-Mas|last4=G|first4=Clot|last5=J|first5=Gutiérrez-Abril|last6=M|first6=Prieto|last7=I|first7=Ribera-Cortada|last8=R|first8=Woroniecka|last9=G|first9=Rymkiewicz|date=2019|title=CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1 - mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30538135/|language=en|doi=10.1182/blood-2018-07-862151|pmc=PMC6396173|pmid=30538135}}</ref>
==Links==
==Links==
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==References==
==References==
−(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
+(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />
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==Notes==
==Notes==
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<nowiki>*</nowiki>''Citation of this Page'': “Mantle cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Mantle_cell_lymphoma</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Mantle cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Mantle_cell_lymphoma</nowiki>.
−[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]]
+[[Category:HAEM5]]
+[[Category:DISEASE]]
+[[Category:Diseases M]]