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(General Instructions – The ~~main~~ focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ HUGO-approved gene names and symbols] (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 [[Author_Instructions]] and [[Frequently Asked Questions (FAQs)|FAQs]] as well as contact your [[Leadership|Associate Editor]] or [mailto:CCGA@cancergenomics.org Technical Support])

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(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/ HUGO-approved gene names and symbols] (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 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 [[Author_Instructions]] and [[Frequently Asked Questions (FAQs)|FAQs]] as well as contact your [[Leadership|Associate Editor]] or [mailto:CCGA@cancergenomics.org Technical Support].)

==Primary Author(s)*==

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==~~Chromosomal Rearrangements~~ (~~Gene Fusions~~)==

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==WHO Essential and Desirable Genetic Diagnostic Criteria==

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(''Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; 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.'')

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{| class="wikitable"

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|WHO Essential Criteria (Genetics)*

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|WHO Desirable Criteria (Genetics)*

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|Other Classification

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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 WHO Classification of Tumours].

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==Related Terminology==

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(''Instructions: The table will have the related terminology from the WHO autocompleted.)''

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|Acceptable

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|Not Recommended

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~~Put your text here and fill in the table~~

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==Gene Rearrangements==

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Put your text here and fill in the table (''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.'')

{| class="wikitable sortable"

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!~~Chromosomal Rearrangement~~!!~~Genes in~~ Fusion (~~5’ or 3’ Segments~~)!!~~Pathogenic Derivative~~!!Prevalence

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!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)

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!Diagnostic Significance ~~(Yes~~, ~~No or Unknown)~~

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!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)

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!~~Prognostic~~ Significance (Yes, No ~~or Unknown~~)

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!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

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!~~Therapeutic Significance~~ (Yes, ~~No or Unknown~~)

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!Established Clinical Significance Per Guidelines - Yes or No (Source)

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~~!Notes~~

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!Clinical Relevance Details/Other Notes

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|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)

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|EXAMPLE: Common (CML)

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|EXAMPLE: D, P, T

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|EXAMPLE: Yes (WHO, NCCN)

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|EXAMPLE:

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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).

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|EXAMPLE: ~~t(9;22)(q34;q11.2)|~~|EXAMPLE: 3'~~ABL1 / 5~~'~~BCR|~~|EXAMPLE: ~~der(22)|~~|EXAMPLE: ~~20%~~ (~~COSMIC~~)

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|EXAMPLE: ''CIC''

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EXAMPLE: ~~30%~~ (~~add reference~~)

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|EXAMPLE: ''CIC::DUX4''

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|~~Yes~~

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|EXAMPLE: 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''.

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~~|No~~

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|EXAMPLE: t(4;19)(q25;q13)

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|~~Yes~~

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|EXAMPLE: Common (CIC-rearranged sarcoma)

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|EXAMPLE: D

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|EXAMPLE:

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~~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~~).

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''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).

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|EXAMPLE: ''ALK''

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|EXAMPLE: ''ELM4::ALK''

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

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|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.

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|EXAMPLE: N/A

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|EXAMPLE: Rare (Lung adenocarcinoma)

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|EXAMPLE: T

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|EXAMPLE:

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

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|EXAMPLE: ''ABL1''

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|EXAMPLE: N/A

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|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.

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|EXAMPLE: N/A

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|EXAMPLE: Recurrent (IDH-wildtype Glioblastoma)

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|EXAMPLE: D, P, T

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<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>

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==Individual Region Genomic Gain / Loss / LOH==

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==Individual Region Genomic Gain/Loss/LOH==

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Put your text here and fill in the table (''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.'')

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Put your text here and fill in the table (''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.'')

{| class="wikitable sortable"

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!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!~~Minimal Region Cytoband~~

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!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''

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!Diagnostic ~~Significance (Yes~~, ~~No or Unknown)~~

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!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''

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!Prognostic Significance ~~(Yes~~, ~~No or Unknown)~~

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!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

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!~~Therapeutic~~ Significance (Yes, No ~~or Unknown~~)

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!'''Clinical Relevance Details/Other Notes'''

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!Notes

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|EXAMPLE:

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7

|EXAMPLE: Loss

|EXAMPLE:

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chr7

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chr7~~:1- 159,335,973 [hg38]~~

|EXAMPLE:

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Unknown

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~~chr7~~

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|EXAMPLE: D, P

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~~|Yes~~

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|EXAMPLE: No

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|~~Yes~~

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|No

|EXAMPLE:

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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).

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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~~).

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|EXAMPLE:

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8

|EXAMPLE: Gain

|EXAMPLE:

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chr8

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~~chr8~~:1-~~145~~,~~138~~,~~636~~ [hg38]

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|EXAMPLE:

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Unknown

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|EXAMPLE: D, P

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|EXAMPLE:

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

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|EXAMPLE:

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17

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|EXAMPLE: Amp

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|EXAMPLE:

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17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]

|EXAMPLE:

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''ERBB2''

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~~chr8~~

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|EXAMPLE: D, P, T

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~~|No~~

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|No

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|No

|EXAMPLE:

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

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

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==Characteristic Chromosomal Patterns==

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==Characteristic Chromosomal or Other Global Mutational Patterns==

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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. Do not delete table.'')

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Put your text here and fill in the table (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.'')

{| class="wikitable sortable"

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!Chromosomal Pattern

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!~~Diagnostic Significance (Yes~~, No or ~~Unknown~~)

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!Molecular Pathogenesis

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!Prognostic Significance ~~(Yes~~, ~~No or Unknown)~~

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!'''Prevalence -'''

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!~~Therapeutic~~ Significance (Yes, No ~~or Unknown~~)

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'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''

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!Notes

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!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''

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!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

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!'''Clinical Relevance Details/Other Notes'''

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|EXAMPLE:

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Co-deletion of 1p and 18q

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|~~Yes~~

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|EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

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|No

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|EXAMPLE: Common (Oligodendroglioma)

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|No

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|EXAMPLE: D, P

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|EXAMPLE:

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Microsatellite instability - hypermutated

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~~See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma~~ (~~add reference~~).

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|EXAMPLE: Common (Endometrial carcinoma)

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|EXAMPLE: P, T

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</blockquote>

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==Gene Mutations (SNV / INDEL)==

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==Gene Mutations (SNV/INDEL)==

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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 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.'')

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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. 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.'')

{| 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 -'''

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!'''~~Diagnostic~~ Significance (Yes, No ~~or Unknown~~)'''

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'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''

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!~~Prognostic Significance (Yes, No or Unknown)~~

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!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T '''

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~~!Therapeutic Significance (Yes, No or Unknown)~~

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!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

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!Notes

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!'''Clinical Relevance Details/Other Notes'''

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|EXAMPLE: ~~TP53; Variable LOF mutations~~

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|EXAMPLE:''EGFR''

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EXAMPLE:

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|EXAMPLE: Exon 18-21 activating mutations

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~~EGFR;~~ Exon 20 mutations

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|EXAMPLE: Oncogene

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|EXAMPLE: Common (lung cancer)

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EXAMPLE: ~~BRAF; Activating~~ mutations

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|EXAMPLE: T

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|EXAMPLE: ~~TSG~~

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|EXAMPLE: Yes (NCCN)

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|EXAMPLE: ~~20%~~ (~~COSMIC~~)

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|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 (add references).

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EXAMPLE: 30% (add ~~Reference~~)

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|EXAMPLE: ''TP53''; Variable LOF mutations

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|EXAMPLE: ~~IDH1 R123H~~

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|EXAMPLE: ~~EGFR amplification~~

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|EXAMPLE: Variable LOF mutations

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|EXAMPLE: Tumor Supressor Gene

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|EXAMPLE: Common (breast cancer)

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|EXAMPLE: P

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

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|EXAMPLE: ''BRAF''; Activating mutations

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|EXAMPLE: Activating mutations

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|EXAMPLE: Oncogene

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|EXAMPLE: Common (melanoma)

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|EXAMPLE: T

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~~|EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).~~

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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ cBioportal], [https://cancer.sanger.ac.uk/cosmic COSMIC], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

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~~ ~~

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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>

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</blockquote>

==Epigenomic Alterations==

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Put your text here

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==Genes and Main Pathways Involved==

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~~==Genes and Main Pathways Involved==~~

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

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

{| class="wikitable sortable"

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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

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|EXAMPLE: BRAF and MAP2K1; Activating mutations

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|EXAMPLE: ''BRAF'' and ''MAP2K1''; Activating mutations

|EXAMPLE: MAPK signaling

|EXAMPLE: Increased cell growth and proliferation

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|EXAMPLE: CDKN2A; Inactivating mutations

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|EXAMPLE: ''CDKN2A''; Inactivating mutations

|EXAMPLE: Cell cycle regulation

|EXAMPLE: Unregulated cell division

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|EXAMPLE: ~~KMT2C~~ and ARID1A; Inactivating mutations

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|EXAMPLE: ''KMT2C'' and ''ARID1A''; Inactivating mutations

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|EXAMPLE: ~~Histone~~ modification, chromatin remodeling

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|EXAMPLE: Histone modification, chromatin remodeling

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|EXAMPLE: ~~Abnormal~~ gene expression program

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|EXAMPLE: Abnormal gene expression program

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==References==

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(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. ~~The reference list in this section will be automatically generated and sorted.'' ''~~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''''.'') <references />

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(use the "Cite" icon at the top of the page) (''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''''.'') <references />

'''

Bailey.Glen

Autochecked users, Comment administrators, Editors, Interface administrators, Reviewers, Suppressors, Administrators, Widget editors

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