Compendium of Cancer Genome Aberrations

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HAEM5:B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion (view source)

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{{DISPLAYTITLE:B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion}}
 
{{DISPLAYTITLE:B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion}}
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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
    
{{Under Construction}}
 
{{Under Construction}}
   −
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-04. The original page can be found at [[HAEM4:B-Lymphoblastic Leukemia/Lymphoma with t(1;19)(q23;p13.3); TCF3-PBX1]].
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<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:B-Lymphoblastic Leukemia/Lymphoma with t(1;19)(q23;p13.3); TCF3-PBX1]].
 
}}</blockquote>
 
}}</blockquote>
 +
 +
<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)*==
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Linda D. Cooley, MD, MBA. Children's Mercy Kansas City, Kansas City, MO
 
Linda D. Cooley, MD, MBA. Children's Mercy Kansas City, Kansas City, MO
 +
==WHO Classification of Disease==
   −
__TOC__
+
{| class="wikitable"
 +
!Structure
 +
!Disease
 +
|-
 +
|Book
 +
|Haematolymphoid Tumours (5th ed.)
 +
|-
 +
|Category
 +
|B-cell lymphoid proliferations and lymphomas
 +
|-
 +
|Family
 +
|Precursor B-cell neoplasms
 +
|-
 +
|Type
 +
|B-lymphoblastic leukaemias/lymphomas
 +
|-
 +
|Subtype(s)
 +
|B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion
 +
|}
   −
==Cancer Category / Type==
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==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>
−
B-Lymphoblastic Leukemia/Lymphoma
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{| class="wikitable"
−
 
+
|+
−
==Cancer Sub-Classification / Subtype==
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|WHO Essential Criteria (Genetics)*
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+
|
−
B-Lymphoblastic Leukemia/Lymphoma with t(1;19)(q23;p13.3); ''TCF3-PBX1''
+
|-
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|WHO Desirable Criteria (Genetics)*
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==Definition / Description of Disease==
+
|
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Neoplasm of B-cell lineage precursor lymphoblasts where the blasts contain a translocation between ''PBX1'' at 1q23 and ''TCF3'' at 19p13.3.<ref name=":1">Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017</ref>
+
|-
−
 
+
|Other Classification
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==Synonyms / Terminology==
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|
−
 
+
|}
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''TCF3'' is also known as ''E2A.''
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<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==
−
==Epidemiology / Prevalence==
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<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
−
 
  −
The t(1;19) translocation is present in ~5% pediatric and ~3% adult B-ALL cases. The incidence of this translocation does not vary significantly with age, however, there is a high incidence (~12%) of this rearrangement in African-American children with B-ALL.<ref name=":0">{{Cite journal|last=Akkari|first=Yassmine M. N.|last2=Bruyere|first2=Helene|last3=Hagelstrom|first3=R. Tanner|last4=Kanagal-Shamanna|first4=Rashmi|last5=Liu|first5=Jie|last6=Luo|first6=Minjie|last7=Mikhail|first7=Fady M.|last8=Pitel|first8=Beth A.|last9=Raca|first9=Gordana|date=05 2020|title=Evidence-based review of genomic aberrations in B-lymphoblastic leukemia/lymphoma: Report from the cancer genomics consortium working group for lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/32302940|journal=Cancer Genetics|volume=243|pages=52–72|doi=10.1016/j.cancergen.2020.03.001|issn=2210-7762|pmid=32302940}}</ref>
  −
 
  −
==Clinical Features==
  −
 
  −
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
   
{| class="wikitable"
 
{| class="wikitable"
−
|'''Signs and Symptoms'''
+
|+
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|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
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|Acceptable
−
 
+
|
−
EXAMPLE B-symptoms (weight loss, fever, night sweats)
  −
 
  −
EXAMPLE Fatigue
  −
 
  −
EXAMPLE Lymphadenopathy (uncommon)
   
|-
 
|-
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|'''Laboratory Findings'''
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|Not Recommended
−
|EXAMPLE Cytopenias
+
|
−
 
  −
EXAMPLE Lymphocytosis (low level)
   
|}
 
|}
    +
==Gene Rearrangements==
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<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
  −
  −
No unique clinical features that distinguish this entity from other types of B-ALL. Common clinical features of B-ALL include:
  −
  −
*Fatigue
  −
*Infections
  −
*Easy bruising/bleeding
  −
  −
Other symptoms present may include:
  −
  −
*Achiness
  −
*Fever
  −
*Night sweats
  −
*Weight loss
  −
  −
These features manifest clinically as anemia, neutropenia, and/or thrombocytopenia. <ref name=":0" />
  −
  −
</blockquote>
  −
==Sites of Involvement==
  −
  −
Bone marrow, Blood, Central Nervous System (CNS) <ref name=":0" />
  −
  −
==Morphologic Features==
  −
  −
There are no unique morphological  features that distinguish this entity from other types of ALL.<ref name=":1" />
  −
  −
==Immunophenotype==
  −
  −
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
      +
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 (universal)||EXAMPLE CD1
+
|<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 (subset)||EXAMPLE CD2
+
|<span class="blue-text">EXAMPLE:</span> ''CIC''
−
|-
+
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
−
|Negative (universal)||EXAMPLE CD3
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|<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)
 +
|<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).
 
|-
 
|-
−
|Negative (subset)||EXAMPLE CD4
+
|<span class="blue-text">EXAMPLE:</span> ''ALK''
−
|}
+
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
      −
<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
+
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>
   −
Blasts with pre-B phenotype, positive for CD19, CD10 and cytoplasmic mu heavy chain. <ref name=":1" />
+
Both balanced and unbalanced forms are observed by FISH (add references).
−
 
  −
</blockquote>
  −
==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
+
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
−
!Diagnostic Significance (Yes, No or Unknown)
+
|<span class="blue-text">EXAMPLE:</span> N/A
−
!Prognostic Significance (Yes, No or Unknown)
+
|<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.
−
!Therapeutic Significance (Yes, No or Unknown)
+
|<span class="blue-text">EXAMPLE:</span> N/A
−
!Notes
+
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
 +
|<span class="blue-text">EXAMPLE:</span> D, P, T
 +
|
 +
|
 
|-
 
|-
−
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+
|
−
EXAMPLE 30% (add reference)
+
|
−
|Yes
+
|
−
|No
+
|
−
|Yes
+
|
−
|EXAMPLE
+
|
 +
|
 +
|
 +
|}
   −
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).
+
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
−
|}
  −
     −
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
+
The breakpoints of the t(1;19) translocation  typically fall within intron 16 of ''TCF3'' and intron 3 of ''PBX1''. <ref name=":0">{{Cite journal|last=Akkari|first=Yassmine M. N.|last2=Bruyere|first2=Helene|last3=Hagelstrom|first3=R. Tanner|last4=Kanagal-Shamanna|first4=Rashmi|last5=Liu|first5=Jie|last6=Luo|first6=Minjie|last7=Mikhail|first7=Fady M.|last8=Pitel|first8=Beth A.|last9=Raca|first9=Gordana|date=05 2020|title=Evidence-based review of genomic aberrations in B-lymphoblastic leukemia/lymphoma: Report from the cancer genomics consortium working group for lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/32302940|journal=Cancer Genetics|volume=243|pages=52–72|doi=10.1016/j.cancergen.2020.03.001|issn=2210-7762|pmid=32302940}}</ref>
−
 
  −
The breakpoints of the t(1;19) translocation  typically fall within intron 16 of ''TCF3'' and intron 3 of ''PBX1''. <ref name=":0" />
      
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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|}
 
|}
 
 
 +
<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</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>
   −
The t(1;19) diagnosis was associated with high risk and poor prognosis in earlier studies, however, modern intensive chemotherapy has changed this paradigm. A recent (2021) study showed that patients with ''TCF3-PBX1'' had intermediate rates of 5-year event-free survival (80-88.2%). Despite the favorable prognosis of this subtype of ALL, there is an increased relative risk of central nervous system relapse associated with this translocation.  <ref name=":1" /><ref name=":0" /><ref>{{Cite journal|last=Jeha|first=Sima|last2=Choi|first2=John|last3=Roberts|first3=Kathryn G.|last4=Pei|first4=Deqing|last5=Coustan-Smith|first5=Elaine|last6=Inaba|first6=Hiroto|last7=Rubnitz|first7=Jeffrey E.|last8=Ribeiro|first8=Raul C.|last9=Gruber|first9=Tanja A.|date=2021-07|title=Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy|url=https://pubmed.ncbi.nlm.nih.gov/34250504|journal=Blood Cancer Discovery|volume=2|issue=4|pages=326–337|doi=10.1158/2643-3230.bcd-20-0229|issn=2643-3249|pmc=8265990|pmid=34250504}}</ref>
+
The t(1;19) diagnosis was associated with high risk and poor prognosis in earlier studies, however, modern intensive chemotherapy has changed this paradigm. A recent (2021) study showed that patients with ''TCF3-PBX1'' had intermediate rates of 5-year event-free survival (80-88.2%). Despite the favorable prognosis of this subtype of ALL, there is an increased relative risk of central nervous system relapse associated with this translocation.  <ref name=":1">Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017</ref><ref name=":0" /><ref>{{Cite journal|last=Jeha|first=Sima|last2=Choi|first2=John|last3=Roberts|first3=Kathryn G.|last4=Pei|first4=Deqing|last5=Coustan-Smith|first5=Elaine|last6=Inaba|first6=Hiroto|last7=Rubnitz|first7=Jeffrey E.|last8=Ribeiro|first8=Raul C.|last9=Gruber|first9=Tanja A.|date=2021-07|title=Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy|url=https://pubmed.ncbi.nlm.nih.gov/34250504|journal=Blood Cancer Discovery|volume=2|issue=4|pages=326–337|doi=10.1158/2643-3230.bcd-20-0229|issn=2643-3249|pmc=8265990|pmid=34250504}}</ref>
    +
<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 fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
      +
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'''
−
!Prognostic Significance (Yes, No or Unknown)
+
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
−
!Therapeutic Significance (Yes, No or Unknown)
+
!'''Clinical Relevance Details/Other Notes'''
−
!Notes
   
|-
 
|-
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
−
 
   
7
 
7
−
|EXAMPLE Loss
+
|<span class="blue-text">EXAMPLE:</span> Loss
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
−
 
  −
chr7:1- 159,335,973 [hg38]
  −
|EXAMPLE
  −
 
   
chr7
 
chr7
−
|Yes
+
|<span class="blue-text">EXAMPLE:</span>
−
|Yes
+
Unknown
−
|No
+
|<span class="blue-text">EXAMPLE:</span> D, P
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span> No
−
 
+
|<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 reference).
+
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).
 
|-
 
|-
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
−
 
   
8
 
8
−
|EXAMPLE Gain
+
|<span class="blue-text">EXAMPLE:</span> Gain
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
−
 
  −
chr8:1-145,138,636 [hg38]
  −
|EXAMPLE
  −
 
   
chr8
 
chr8
−
|No
+
|<span class="blue-text">EXAMPLE:</span>
−
|No
+
Unknown
−
|No
+
|<span class="blue-text">EXAMPLE:</span> D, P
−
|EXAMPLE
+
|
−
 
+
|<span class="blue-text">EXAMPLE:</span>
−
Common recurrent secondary finding for t(8;21) (add reference).
+
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>
 +
''ERBB2''
 +
|<span class="blue-text">EXAMPLE:</span> D, P, T
 +
|
 +
|<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 somatic copy number aberrations are not frequently seen in ''TCF3-PBX1'' B-ALL
 
Secondary somatic copy number aberrations are not frequently seen in ''TCF3-PBX1'' B-ALL
 +
<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 <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'')</span>
      +
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 -'''
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!Therapeutic Significance (Yes, No or Unknown)
+
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
−
!Notes
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!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
 +
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
 +
!'''Clinical Relevance Details/Other Notes'''
 
|-
 
|-
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
−
 
   
Co-deletion of 1p and 18q
 
Co-deletion of 1p and 18q
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|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
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|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
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|No
+
|<span class="blue-text">EXAMPLE:</span> D, P
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|EXAMPLE:
+
|
−
 
+
|
−
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
+
|-
 +
|<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
 +
|
 +
|
 +
|-
 +
|
 +
|
 +
|
 +
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 +
|
 +
|
 
|}
 
|}
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<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>
    
The t(1;19) translocation can be balanced or unbalanced. The unbalanced form has a der(19) resulting in trisomy of 1q distal to PBX1.<ref name=":2">Meloni-Ehrig A., (2013). The principles of clinical cytogenetics. 3rd edition. Steven L. Gersen and Martha B. Keagle , Editors. Springer. DOI 10.1007/978-1-4419-1688-4. p327-329.</ref>  
 
The t(1;19) translocation can be balanced or unbalanced. The unbalanced form has a der(19) resulting in trisomy of 1q distal to PBX1.<ref name=":2">Meloni-Ehrig A., (2013). The principles of clinical cytogenetics. 3rd edition. Steven L. Gersen and Martha B. Keagle , Editors. Springer. DOI 10.1007/978-1-4419-1688-4. p327-329.</ref>  
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<blockquote class="blockedit">
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<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</blockquote>
 
</blockquote>
−
==Gene Mutations (SNV / INDEL)==
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==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 and common as well 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.'') </span>
      +
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"
 
|-
 
|-
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!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
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!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
−
!'''Diagnostic Significance (Yes, No or Unknown)'''
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'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
−
!Prognostic Significance (Yes, No or Unknown)
+
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''
−
!Therapeutic Significance (Yes, No or Unknown)
+
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
−
!Notes
+
!'''Clinical Relevance Details/Other Notes'''
 
|-
 
|-
−
|EXAMPLE: TP53; Variable LOF mutations
+
|<span class="blue-text">EXAMPLE:</span>''EGFR''
   −
EXAMPLE:
+
<br />
−
 
+
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
−
EGFR; Exon 20 mutations
+
|<span class="blue-text">EXAMPLE:</span> Oncogene
−
 
+
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
−
EXAMPLE: BRAF; Activating mutations
+
|<span class="blue-text">EXAMPLE:</span> T
−
|EXAMPLE: TSG
+
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
−
|EXAMPLE: 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).
−
 
+
|-
−
EXAMPLE: 30% (add Reference)
+
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
−
|EXAMPLE: IDH1 R123H
+
<br />
−
|EXAMPLE: 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
 +
|
 +
|
 +
|-
 +
|
 +
|
 +
|
 +
|
 
|
 
|
 
|
 
|
 
|
 
|
−
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
+
|}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.
−
<br />
  −
|}
  −
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.
  −
 
     −
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+
<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>
    
Secondary somatic DNA mutations are not frequently seen in ''TCF3-PBX1'' B-ALL. <ref name=":0" />
 
Secondary somatic DNA mutations are not frequently seen in ''TCF3-PBX1'' B-ALL. <ref name=":0" />
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|}
 
|}
    +
<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</blockquote>
 
</blockquote>
 
==Epigenomic Alterations==
 
==Epigenomic Alterations==
 +
    
Put your text here
 
Put your text here
 +
==Genes and Main Pathways Involved==
   −
==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.'')</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
 
|-
 
|-
−
|EXAMPLE: BRAF and MAP2K1; Activating mutations
+
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
−
|EXAMPLE: MAPK signaling
+
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
−
|EXAMPLE: 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> Cell cycle regulation
 +
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 
|-
 
|-
−
|EXAMPLE: CDKN2A; Inactivating mutations
+
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
−
|EXAMPLE: Cell cycle regulation
+
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
−
|EXAMPLE: Unregulated cell division
+
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
 
|-
 
|-
−
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+
|
−
|EXAMPLE:  Histone modification, chromatin remodeling
+
|
−
|EXAMPLE:  Abnormal gene expression program
+
|
 
|}
 
|}
   −
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+
<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>
    
''TCF3'' gene at 19p13.3 is important during early lymphocyte development, whereas ''PBX1'' at 1q23 is a component of a transcriptional complex that regulates embryogenesis and hematopoiesis. Fusion protein resulting from the TCF3-PBX1 translocation is a transcriptional activator which likely interferes with the normal function of these genes. Expression of this fusion protein is thought to interfere with key regulatory pathways such as WNT and apoptosis/cell cycle control pathways which may drive a leukemic process. The DNA-binding and protein dimerization domains of PBX1 replaces the TCF3 helix-loop-helix DNA-binding motif in ''TCF3-PBX1'' fusion. The remaining transcriptional activating domains of TCF3 leads to constitutive nuclear localization and transformation of PBX1 into an oncogenic transcriptional factor <ref>{{Cite journal|last=Diakos|first=Christofer|last2=Xiao|first2=Yuanyuan|last3=Zheng|first3=Shichun|last4=Kager|first4=Leo|last5=Dworzak|first5=Michael|last6=Wiemels|first6=Joseph L.|date=2014|title=Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein|url=https://pubmed.ncbi.nlm.nih.gov/24503810|journal=PloS One|volume=9|issue=2|pages=e87602|doi=10.1371/journal.pone.0087602|issn=1932-6203|pmc=3913655|pmid=24503810}}</ref><ref name=":1" /><ref name=":0" />
 
''TCF3'' gene at 19p13.3 is important during early lymphocyte development, whereas ''PBX1'' at 1q23 is a component of a transcriptional complex that regulates embryogenesis and hematopoiesis. Fusion protein resulting from the TCF3-PBX1 translocation is a transcriptional activator which likely interferes with the normal function of these genes. Expression of this fusion protein is thought to interfere with key regulatory pathways such as WNT and apoptosis/cell cycle control pathways which may drive a leukemic process. The DNA-binding and protein dimerization domains of PBX1 replaces the TCF3 helix-loop-helix DNA-binding motif in ''TCF3-PBX1'' fusion. The remaining transcriptional activating domains of TCF3 leads to constitutive nuclear localization and transformation of PBX1 into an oncogenic transcriptional factor <ref>{{Cite journal|last=Diakos|first=Christofer|last2=Xiao|first2=Yuanyuan|last3=Zheng|first3=Shichun|last4=Kager|first4=Leo|last5=Dworzak|first5=Michael|last6=Wiemels|first6=Joseph L.|date=2014|title=Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein|url=https://pubmed.ncbi.nlm.nih.gov/24503810|journal=PloS One|volume=9|issue=2|pages=e87602|doi=10.1371/journal.pone.0087602|issn=1932-6203|pmc=3913655|pmid=24503810}}</ref><ref name=":1" /><ref name=":0" />
    +
<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</blockquote>
 
</blockquote>
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
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==Familial Forms==
 
==Familial Forms==
 +
    
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
 
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
−
   
==Additional Information==
 
==Additional Information==
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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 />
   −
'''
+
<br />
    
==Notes==
 
==Notes==
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
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<nowiki>*</nowiki>''Citation of this Page'': “B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B_lymphoblastic_leukaemia/lymphoma_with_TCF3::PBX1_fusion</nowiki>.
 
<nowiki>*</nowiki>''Citation of this Page'': “B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B_lymphoblastic_leukaemia/lymphoma_with_TCF3::PBX1_fusion</nowiki>.
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[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases B]]
+
[[Category:HAEM5]]
 +
[[Category:DISEASE]]
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[[Category:Diseases B]]
Retrieved from "https://ccga.io/index.php/Special:MobileDiff/13447...16587"