Difference between revisions of "CNS5:Diffuse leptomeningeal glioneuronal tumour"

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{{Under Construction}}
 
{{Under Construction}}
<span style="color:#0070C0">(''General Instructions – TThe focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge using various 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 will capture the current genetics/genomics knowledge that evolves more rapidly than books can be updated 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/ 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. 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 using various 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 will capture the current genetics/genomics knowledge that evolves more rapidly than books can be updated 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/ 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. 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>
 +
 
 
__TOC__
 
__TOC__
 
==Primary Author(s)*==
 
==Primary Author(s)*==
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|
 
|
 
|}
 
|}
==Definition / Description of Disease==
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==WHO Essential and Desirable Genetic Diagnostic Criteria==
Put your text here <span style="color:#0070C0">(''Instructions: Brief description of approximately one paragraph - include disease context relative to other WHO classification categories, diagnostic criteria if applicable, and differential diagnosis if applicable. Other classifications can be referenced for comparison.'') </span>
+
Put your text here <span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO autopopulated; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.'') </span>
==Synonyms / Terminology==
 
Put your text here <span style="color:#0070C0">(''Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.'') </span>
 
==Epidemiology / Prevalence==
 
Put your text here
 
==Clinical Features==
 
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>
 
 
{| class="wikitable"
 
{| class="wikitable"
|'''Signs and Symptoms'''
+
|WHO  Essential Criteria (Genetics)*
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
+
|
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
+
|-
 
+
|WHO  Desirable Criteria (Genetics)*
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
+
|
 
|-
 
|-
|'''Laboratory Findings'''
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|Other Classification
|<span class="blue-text">EXAMPLE:</span> Cytopenias
+
|
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
 
 
|}
 
|}
==Sites of Involvement==
+
<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/login WHO Classification of Tumours].
Put your text here <span style="color:#0070C0">(''Instruction: Indicate physical sites; <span class="blue-text">EXAMPLE:</span> nodal, extranodal, bone marrow'') </span>
+
 
==Morphologic Features==
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==Related Terminology==
Put your text here <span style="color:#0070C0">(''Instructions: Brief description of typically approximately one paragraph'') </span>
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<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO autopopulated'') </span>
==Immunophenotype==
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{| class="wikitable"
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>
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|Acceptable
{| class="wikitable sortable"
+
|
 
|-
 
|-
!Finding!!Marker
+
|Not  Recommended
|-
+
|
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
 
|-
 
|Positive (subset)||
 
|-
 
|Negative (universal)||
 
|-
 
|Negative (subset)||
 
 
|}
 
|}
==Chromosomal Rearrangements (Gene Fusions)==
+
==Chromosomal Rearrangements==
 
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>
 
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>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
+
!Driver Gene!!'''Fusion(s) and Common Partner Genes'''!!'''Molecular Pathogenesis'''!!'''Typical Chromosomal Alteration(s)'''
!Diagnostic Significance (Yes, No or Unknown)
+
!'''Prevalence - 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, No)'''
 
!Notes
 
!Notes
 
|-
 
|-
|<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)
+
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR''::''ABL1''
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
+
|<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> Yes
+
|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|<span class="blue-text">EXAMPLE:</span> No
+
|<span class="blue-text">EXAMPLE:</span> Common  (CML)
 +
|<span class="blue-text">EXAMPLE:</span> D,  P
 
|<span class="blue-text">EXAMPLE:</span> Yes
 
|<span class="blue-text">EXAMPLE:</span> Yes
 
|<span class="blue-text">EXAMPLE:</span>
 
|<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).
+
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).
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span> ''CIC''
 +
|<span class="blue-text">EXAMPLE:</span> ''CIC''::''DUX4''
 +
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is typically 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).
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span> ''ALK''
 +
|<span class="blue-text">EXAMPLE:</span> ''EML4''::''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> ''EGFRvIII''
 +
|<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
 +
|
 +
|
 +
|-
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 
|}
 
|}
 
==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. Do not delete table.'') </span>
+
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
+
!Chromosome Number!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build; Size]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)
+
!'''Relevant Gene(s)'''
!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, No)'''
 
!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> Whole chromosome
chr7:1-159,335,973 [hg38]
+
|<span class="blue-text">EXAMPLE:</span> chr7
|<span class="blue-text">EXAMPLE:</span>
+
|<span class="blue-text">EXAMPLE:</span> Unknown
chr7
+
|<span class="blue-text">EXAMPLE:</span> D, P
|<span class="blue-text">EXAMPLE:</span> Yes
 
|<span class="blue-text">EXAMPLE:</span> Yes
 
 
|<span class="blue-text">EXAMPLE:</span> No
 
|<span class="blue-text">EXAMPLE:</span> 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 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 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> Whole chromosome
chr8:1-145,138,636 [hg38]
+
|<span class="blue-text">EXAMPLE:</span> chr8
|<span class="blue-text">EXAMPLE:</span>
 
chr8
 
|<span class="blue-text">EXAMPLE:</span> No
 
 
|<span class="blue-text">EXAMPLE:</span> No
 
|<span class="blue-text">EXAMPLE:</span> No
 +
|<span class="blue-text">EXAMPLE:</span> D, P
 
|<span class="blue-text">EXAMPLE:</span> No
 
|<span class="blue-text">EXAMPLE:</span> No
 
|<span class="blue-text">EXAMPLE:</span>
 
|<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 reference).
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span> 17
 +
|<span class="blue-text">EXAMPLE:</span> Amp
 +
|<span class="blue-text">EXAMPLE:</span> chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
 +
|<span class="blue-text">EXAMPLE:</span> 17q12
 +
|
 +
|<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.
 +
|-
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 
|}
 
|}
==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. Do not delete table.'')</span>
+
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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Do not delete 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 -Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
!Therapeutic Significance (Yes, No or Unknown)
+
!'''Diagnostic, Prognostic, and Therapeutic Significance (D, P, T)'''
 +
!'''Established Clinical Significance Per Guidelines (Yes, No)'''
 
!Notes
 
!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
+
|<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).
|<span class="blue-text">EXAMPLE:</span> Yes
+
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|<span class="blue-text">EXAMPLE:</span> No
+
|<span class="blue-text">EXAMPLE:</span> D, P
|<span class="blue-text">EXAMPLE:</span> No
+
|
|<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).
+
|-
 +
|<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
 +
|
 +
|
 +
|-
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 
|}
 
|}
 
==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 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>
+
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. 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. Can include concomitant and mutually exclusive mutations in the notes section. Do not delete 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 (TSG)/Oncogene/Other'''!!'''Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''!!'''Diagnostic, Prognostic, and Therapeutic Significance (D, P, T)'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
+
!'''Established Clinical Significance Per Guidelines (Yes, No)'''
!Prognostic Significance (Yes, No or Unknown)
 
!Therapeutic Significance (Yes, No or Unknown)
 
 
!Notes
 
!Notes
 
|-
 
|-
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
+
|<span class="blue-text">EXAMPLE:</span> ''TP53''
<span class="blue-text">EXAMPLE:</span>
+
<br />
 +
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
 +
|<span class="blue-text">EXAMPLE:</span> TSG
 +
|<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>
  
''EGFR''; Exon 20 mutations
+
''EGFR''
 +
|<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> T
 +
|
 +
|<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.
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span>
  
<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
+
''BRAF''
|<span class="blue-text">EXAMPLE:</span> TSG
+
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
+
|<span class="blue-text">EXAMPLE:</span> Oncogene
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
+
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> ''IDH1'' R123H
+
|<span class="blue-text">EXAMPLE:</span> T
|<span class="blue-text">EXAMPLE:</span> ''EGFR'' amplification
+
|
|<span class="blue-text">EXAMPLE:</span> Yes
+
|
|<span class="blue-text">EXAMPLE:</span> No
+
|-
|<span class="blue-text">EXAMPLE:</span> No
+
|
|<span class="blue-text">EXAMPLE:</span> Excludes hairy cell leukemia (HCL) (add reference).
+
|
 +
|
 +
|
 +
|
 +
|
 +
|
 
|}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.
 
|}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.
 
==Epigenomic Alterations==
 
==Epigenomic Alterations==
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|}
 
|}
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
Put your text here
+
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
 
==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>
Line 187: Line 262:
 
Put your text here
 
Put your text here
 
==Links==
 
==Links==
(use the "Link" icon that looks like two overlapping circles at the top of the page) <span style="color:#0070C0">(''Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
+
(use the "Link" icon that looks like two overlapping circles at the top of the page) <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
 
==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>
+
(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. 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>
 
==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.
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<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 [[Leadership|''Associate Editor'']] or other CCGA representativeWhen pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
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Prior Author(s):

Latest revision as of 13:39, 11 September 2024

(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 using various 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 will capture the current genetics/genomics knowledge that evolves more rapidly than books can be updated 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 HUGO-approved gene names and symbols (italicized when appropriate), 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. 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.

Primary Author(s)*

Put your text here (EXAMPLE: Jane Smith, PhD)

WHO Classification of Disease

(Instructions: This table’s content will be autogenerated.)

Structure Disease
Book
Category
Family
Type
Subtype(s)

WHO Essential and Desirable Genetic Diagnostic Criteria

Put your text here (Instructions: The table will have the diagnostic criteria from the WHO autopopulated; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.)

WHO Essential Criteria (Genetics)*
WHO Desirable Criteria (Genetics)*
Other Classification

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

Related Terminology

(Instructions: The table will have the related terminology from the WHO autopopulated)

Acceptable
Not Recommended

Chromosomal Rearrangements

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)

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, No) Notes
EXAMPLE: ABL1 EXAMPLE: BCR::ABL1 EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1. EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: Common (CML) EXAMPLE: D, P EXAMPLE: 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).

EXAMPLE: CIC EXAMPLE: CIC::DUX4 EXAMPLE: Typically, the last exon of CIC is fused to DUX4. The fusion breakpoint in CIC is typically intra-exonic and removes an inhibitory sequence, upregulating PEA3 genes downstream of CIC including ETV1, ETV4, and ETV5. EXAMPLE: t(4;19)(q25;q13) EXAMPLE: Common (CIC-rearranged sarcoma) EXAMPLE: D EXAMPLE:

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).

EXAMPLE: ALK EXAMPLE: EML4::ALK


Other fusion partners include KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1

EXAMPLE: 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. EXAMPLE: N/A EXAMPLE: Rare (Lung adenocarcinoma) EXAMPLE: T EXAMPLE:

Both balanced and unbalanced forms are observed by FISH (add references).

EXAMPLE: EGFRvIII EXAMPLE: N/A EXAMPLE: 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. EXAMPLE: N/A EXAMPLE: Recurrent (IDH-wildtype Glioblastoma) EXAMPLE: D, P, T

Individual Region Genomic Gain / Loss / LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.)

Chromosome Number Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build; Size] Minimal Region Cytoband Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance (D, P, T) Established Clinical Significance Per Guidelines (Yes, No) Notes
EXAMPLE: 7 EXAMPLE: Loss EXAMPLE: Whole chromosome EXAMPLE: chr7 EXAMPLE: Unknown EXAMPLE: D, P EXAMPLE: No EXAMPLE:

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).

EXAMPLE: 8 EXAMPLE: Gain EXAMPLE: Whole chromosome EXAMPLE: chr8 EXAMPLE: No EXAMPLE: D, P EXAMPLE: No EXAMPLE:

Common recurrent secondary finding for t(8;21) (add reference).

EXAMPLE: 17 EXAMPLE: Amp EXAMPLE: chr17:39,700,064-39,728,658 [hg38; 28.6 kb] EXAMPLE: 17q12 EXAMPLE: D, P, T EXAMPLE:

Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

Characteristic Chromosomal or Other Global Mutational Patterns

Put your text here (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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Do not delete table.)

Chromosomal Pattern Molecular Pathogenesis Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) Diagnostic, Prognostic, and Therapeutic Significance (D, P, T) Established Clinical Significance Per Guidelines (Yes, No) Notes
EXAMPLE: Co-deletion of 1p and 18q EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). EXAMPLE: Common (Oligodendroglioma) EXAMPLE: D, P
EXAMPLE: Microsatellite instability - hypermutated EXAMPLE: Common (Endometrial carcinoma) EXAMPLE: P, T

Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (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. 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. Can include concomitant and mutually exclusive mutations in the notes section. Do not delete table.)

Gene Genetic Alteration Tumor Suppressor Gene (TSG)/Oncogene/Other Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease) Diagnostic, Prognostic, and Therapeutic Significance (D, P, T) Established Clinical Significance Per Guidelines (Yes, No) Notes
EXAMPLE: TP53


EXAMPLE: Variable LOF mutations EXAMPLE: TSG EXAMPLE: Common (breast cancer) EXAMPLE: P EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
EXAMPLE:

EGFR

EXAMPLE: Exon 18-21 activating mutations EXAMPLE: Oncogene EXAMPLE: Common (lung cancer) EXAMPLE: T EXAMPLE: 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.
EXAMPLE:

BRAF

EXAMPLE: Activating mutations EXAMPLE: Oncogene EXAMPLE: Common (melanoma) EXAMPLE: T

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.

Epigenomic Alterations

Put your text here

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete table.)

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE: KMT2C and ARID1A; Inactivating mutations EXAMPLE: Histone modification, chromatin remodeling EXAMPLE: Abnormal gene expression program

Genetic Diagnostic Testing Methods

Put your text here (Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.)

Familial Forms

Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

Put your text here

Links

(use the "Link" icon that looks like two overlapping circles at the top of the page) (Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)

References

(use the "Cite" icon at the top of the page) (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. 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.)

Notes

*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 Associate Editor or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

Prior Author(s):