Compendium of Cancer Genome Aberrations

HAEM5:Primary cutaneous gamma/delta T-cell lymphoma: Difference between revisions

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{{DISPLAYTITLE:Primary cutaneous gamma/delta T-cell lymphoma}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
{{Under Construction}}
<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)*==


Mahzad Azimpouran, MD; Sumire Kitahara, MD; Cedars-Sinai, Los Angeles, CA
Mahzad Azimpouran, MD; Sumire Kitahara, MD; Cedars-Sinai, Los Angeles, CA
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|+
|Acceptable
|Acceptable
|N/A
|N/A
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==Gene Rearrangements==
==Gene Rearrangements==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
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|-
|-
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!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|'''CDKN2A'''||—||Homozygous or biallelic deletion → loss of  p16^INK4A/p14^ARF function (cell‑cycle control)||Tumour suppressor
|'''Common''' (>20%) (~61% in cohort)<ref name=":0">{{Cite journal|last=Daniels|first=Jay|last2=Doukas|first2=Peter G.|last3=Escala|first3=Maria E. Martinez|last4=Ringbloom|first4=Kimberly G.|last5=Shih|first5=David J. H.|last6=Yang|first6=Jingyi|last7=Tegtmeyer|first7=Kyle|last8=Park|first8=Joonhee|last9=Thomas|first9=Jane J.|date=2020-04-14|title=Cellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/32286303|journal=Nature Communications|volume=11|issue=1|pages=1806|doi=10.1038/s41467-020-15572-7|issn=2041-1723|pmc=7156460|pmid=32286303}}</ref>
|P
|No
|High‐frequency  deletion, suggests aggressive biology and may be a prognostic marker<ref name=":0" />
|-
|'''ARID1A'''
|—
|Deletion/truncating mutation → loss of chromatin‑remodelling  function
|Tumour suppressor
|Recurrent (5‑20%) (~28%) (PMC)
|Other / P
|No
|Indicates involvement of epigenetic/chromatin pathways in  PCGDTCL<ref name=":0" />
|-
|'''FAS'''
|—
|Focal or biallelic deletion → loss of apoptosis  signalling via FAS‑FASL pathway
|Tumour suppressor / apoptotic regulator
|Recurrent (5‑20%) (~22%) (PMC)
|Other / P
|No
|Loss of FAS may contribute to immune‐escape of malignant γδ T‑cells<ref name=":0" />
|-
|'''PDCD1'''
|—
|Deletion → loss of PD‑1 (immune‐checkpoint) regulatory  function
|Tumour suppressor / immune‑regulator
|Recurrent (5‑20%) (~22%) (PMC)
|Other / P
|No
|Suggests immune‐escape  mechanism; potential implications for checkpoint therapy though unproven<ref name=":0" />
|-
|'''STAT5B'''
|—
|Activating missense (e.g., N642H) → constitutive STAT5B  signalling (JAK/STAT pathway)
|Oncogene
|Recurrent (5‑20%) (JAK/STAT mutations ~21%)
|T / P
|No
|JAK/STAT pathway dependency; early data suggest JAK‐inhibitor sensitivity in  analogous T‑cell neoplasms; investigational in PCGDTCL<ref name=":1">{{Cite journal|last=Küçük|first=Can|last2=Jiang|first2=Bei|last3=Hu|first3=Xiaozhou|last4=Zhang|first4=Wenyan|last5=Chan|first5=John K. C.|last6=Xiao|first6=Wenming|last7=Lack|first7=Nathan|last8=Alkan|first8=Can|last9=Williams|first9=John C.|date=2015-01-14|title=Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells|url=https://pubmed.ncbi.nlm.nih.gov/25586472|journal=Nature Communications|volume=6|pages=6025|doi=10.1038/ncomms7025|issn=2041-1723|pmc=7743911|pmid=25586472}}</ref>
|-
|'''STAT3'''
|—
|Activating missense → constitutive STAT3 signalling  (JAK/STAT cascade)
|Oncogene
|Rare (<5%) to Recurrent (~5‑20%)
|T / P
|No
|Part of JAK/STAT alterations; less frequent than STAT5B  in PCGDTCL<ref name=":1" />
|-
|'''JAK3'''
|—
|Activating mutation (e.g., R657W) → JAK3 tyrosine kinase  activation (JAK/STAT pathway)
|Oncogene
|Rare (<5%)
|T
|No
|Supports JAK/STAT pathway involvement; therapeutic  relevance remains investigational in this disease<ref name=":0" />
|-
|'''KRAS'''
|—
|Activating hotspot mutations (e.g., G12D, Q61H) →  RAS/MAPK pathway activation
|Oncogene
|Recurrent (5‑20%)
|T / P
|No
|MAPK pathway potentially targetable; mutations associated  with poorer outcome in the cohort studied<ref name=":0" />
|-
|'''NRAS'''
|—
|Activating hotspot mutation → RAS/MAPK pathway activation
|Oncogene
|Rare (<5%) to Recurrent (~5‑20%)
|T / P
|No
|Part of same pathway as KRAS though less common<ref name=":0" />
|-
|'''MYC'''
|—
|Activating missense mutation (e.g., P74L) → MYC pathway  up‑regulation
|Oncogene
|Rare (<5%)
|P / T
|No
|MYC pathway involvement may contribute to more aggressive  phenotype; direct targeting not yet established<ref name=":0" />
|-
|'''MYCN'''
|—
|Activating mutation (e.g., G34R) → MYCN pathway  activation
|Oncogene
|Rare (<5%)
|P / T
|No
|Highlights involvement of MYC family beyond MYC itself in  PCGDTCL<ref name=":0" />
|-
|-
|'''Arm‑level chromosomal alterations (e.g., 9p,  18q deletions; 1q, 7q,15q gains)'''
|'''Arm‑level chromosomal alterations (e.g., 9p,  18q deletions; 1q, 7q,15q gains)'''
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|D / P
|D / P
|No
|No
|These structural changes suggest genomic instability and  aggressive biology; may help risk stratification though not diagnostic per se<ref name=":0" />
|These structural changes suggest genomic instability and  aggressive biology; may help risk stratification though not diagnostic per se<ref name=":0">{{Cite journal|last=Daniels|first=Jay|last2=Doukas|first2=Peter G.|last3=Escala|first3=Maria E. Martinez|last4=Ringbloom|first4=Kimberly G.|last5=Shih|first5=David J. H.|last6=Yang|first6=Jingyi|last7=Tegtmeyer|first7=Kyle|last8=Park|first8=Joonhee|last9=Thomas|first9=Jane J.|date=2020-04-14|title=Cellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/32286303|journal=Nature Communications|volume=11|issue=1|pages=1806|doi=10.1038/s41467-020-15572-7|issn=2041-1723|pmc=7156460|pmid=32286303}}</ref>
|-
|-
|'''Fusion: FYN :: (probable partner TRAF3IP2)'''
|'''Fusion: FYN :: (probable partner TRAF3IP2)'''
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|}
|}
==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|9p
|1p
|Loss (deletion)
|9p21.3 (~ chr9:21,900,000‑22,200,000)
|CDKN2A, CDKN2B
|P
|No
|High‐frequency  homozygous or biallelic deletion (~61% of cases; 45% biallelic) in PCGDTCL. (PMC)  Suggests aggressive biology, prognostic marker candidate<ref name=":0" />
|-
|18q
|Loss
|Loss
|18q (arm level; no precise minimal region specified)
|1p36.11
|Putative tumour suppressors (unspecified)
|ARID1A
|P
|P
|No
|No
|Recurrent deletion ~22% in PCGDTCL cohort. May reflect genomic instability and poor outcome<ref name=":0" />
|Deleted in ~28% of cases. Indicates epigenetic/chromatin modifier pathway involvement<ref name=":0" />
|-
|-
|1q
|1q
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|Amplification in ~33% of cases. Potential gene dosage effect; specific driver gene not yet defined<ref name=":0" />
|Amplification in ~33% of cases. Potential gene dosage effect; specific driver gene not yet defined<ref name=":0" />
|-
|-
|15q
|2q
|Gain (arm‐level)
|Loss
|15q (approx chr15:30,000,000‑102,000,000)
|2q37.3
|Multiple genes on 15q (unspecified)
|PDCD1
|P
|P
|No
|No
|Amplification in ~33% of cases. Likely reflects tumour evolution rather than diagnostic biomarker<ref name=":0" />
|Deletion in ~22% of cases. Immune checkpoint gene loss; potential therapeutic‑escape mechanism<ref name=":0" />
|-
|-
|7q
|7q
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|Amplification in ~39% of cases. Suggests MAPK/other pathway involvement but specific gene not yet defined.
|Amplification in ~39% of cases. Suggests MAPK/other pathway involvement but specific gene not yet defined.
|-
|-
|Focal deletion: CDKN2A
|9p
|Loss (homozygous/biallelic)
|Loss (deletion)
|within 9p21.3, CDKN2A region
|9p21.3 (~ chr9:21,900,000‑22,200,000)
|CDKN2A
|CDKN2A, CDKN2B
|P
|P
|No
|No
|From GISTIC analysis: CDKN2A deletion in 61% of samples,  45% biallelic.  Key focal region in PCGDTCL<ref name=":0" />
|High‐frequency  homozygous or biallelic deletion (~61% of cases; 45% biallelic) in PCGDTCL. (PMC) Suggests aggressive biology, prognostic marker candidate<ref name=":0" />
|-
|-
|Focal deletion: ARID1A
|10q
|Loss
|Loss
|unspecified (del/trunc)
|10q24.1
|ARID1A
|FAS
|P
|P
|No
|No
|Deleted in ~28% of cases. Indicates epigenetic/chromatin modifier pathway involvement<ref name=":0" />
|Deletion in ~22% of cases. Loss of apoptosis regulator; may contribute to immune‑escape<ref name=":0" />
|-
|-
|Focal deletion: FAS
|15q
|Loss
|Gain (arm‐level)
|unspecified (biallelic)
|15q (approx chr15:30,000,000‑102,000,000)
|FAS
|Multiple genes on 15q (unspecified)
|P
|P
|No
|No
|Deletion in ~22% of cases. Loss of apoptosis regulator; may contribute to immune‑escape<ref name=":0" />
|Amplification in ~33% of cases. Likely reflects tumour evolution rather than diagnostic biomarker<ref name=":0" />
|-
|-
|Focal deletion: PDCD1
|18q
|Loss
|Loss
|unspecified
|18q (arm level; no precise minimal region specified)
|PDCD1
|Putative tumour suppressors (unspecified)
|P
|P
|No
|No
|Deletion in ~22% of cases. Immune checkpoint gene loss; potential therapeutic‑escape mechanism<ref name=":0" />
|Recurrent deletion ~22% in PCGDTCL cohort. May reflect genomic instability and poor outcome<ref name=":0" />
|}
|}
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 
{| class="wikitable sortable"
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|}
==Gene Mutations (SNV/INDEL)==
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
 
{| class="wikitable sortable"
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|-
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|T / P: Therapeutic potential (JAK/STAT inhibition);  Prognostic implication (pathway addiction/resistance)
|T / P: Therapeutic potential (JAK/STAT inhibition);  Prognostic implication (pathway addiction/resistance)
|No
|No
|Mutant STAT5B (especially N642H) shown to induce T‑cell  neoplasia in models; in PCGDTCL JAK/STAT addiction shown clinically <ref name=":1" /><ref name=":3">{{Cite journal|last=Zhang|first=Yue|last2=Yescas|first2=Julia A.|last3=Tefft|first3=Kristy|last4=Ng|first4=Spencer|last5=Qiu|first5=Kevin|last6=Wang|first6=Erica B.|last7=Akhtar|first7=Shifa|last8=Walker|first8=Addie|last9=Welborn|first9=Macartney|date=2025-04-15|title=Addiction of primary cutaneous γδ T cell lymphomas to JAK/STAT signaling|url=https://pubmed.ncbi.nlm.nih.gov/40231467|journal=The Journal of Clinical Investigation|volume=135|issue=8|pages=e180417|doi=10.1172/JCI180417|issn=1558-8238|pmc=11996904|pmid=40231467}}</ref>
|Mutant STAT5B (especially N642H) shown to induce T‑cell  neoplasia in models; in PCGDTCL JAK/STAT addiction shown clinically <ref name=":1">{{Cite journal|last=Küçük|first=Can|last2=Jiang|first2=Bei|last3=Hu|first3=Xiaozhou|last4=Zhang|first4=Wenyan|last5=Chan|first5=John K. C.|last6=Xiao|first6=Wenming|last7=Lack|first7=Nathan|last8=Alkan|first8=Can|last9=Williams|first9=John C.|date=2015-01-14|title=Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells|url=https://pubmed.ncbi.nlm.nih.gov/25586472|journal=Nature Communications|volume=6|pages=6025|doi=10.1038/ncomms7025|issn=2041-1723|pmc=7743911|pmid=25586472}}</ref><ref name=":3">{{Cite journal|last=Zhang|first=Yue|last2=Yescas|first2=Julia A.|last3=Tefft|first3=Kristy|last4=Ng|first4=Spencer|last5=Qiu|first5=Kevin|last6=Wang|first6=Erica B.|last7=Akhtar|first7=Shifa|last8=Walker|first8=Addie|last9=Welborn|first9=Macartney|date=2025-04-15|title=Addiction of primary cutaneous γδ T cell lymphomas to JAK/STAT signaling|url=https://pubmed.ncbi.nlm.nih.gov/40231467|journal=The Journal of Clinical Investigation|volume=135|issue=8|pages=e180417|doi=10.1172/JCI180417|issn=1558-8238|pmc=11996904|pmid=40231467}}</ref>
|-
|-
|'''STAT3'''
|'''STAT3'''
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|P / T
|P / T
|No
|No
|MYC pathway involvement may contribute to the aggressive  phenotype; direct targeting not yet established.
|MYC pathway involvement may contribute to the aggressive  phenotype; direct targeting not yet established<ref name=":0" />
|-
|-
|'''MYCN'''
|'''MYCN'''
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|P / T
|P / T
|No
|No
|Highlights involvement of MYC‑family beyond MYC itself in  this disease.
|Highlights involvement of MYC‑family beyond MYC itself in  this disease<ref name=":0" />
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}Note: A more extensive list of mutations can be found in [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.
==Epigenomic Alterations==
==Epigenomic Alterations==
Put your text here
N/A
==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
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"
|-
|-
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|-
|-
|DNMT3A (DNA methyltransferase)
|DNMT3A (DNA methyltransferase)
|Loss‑of‑function mutations or deletions → reduced de novo  DNA methylation; “epigenetic writer” defect (DNA methylation pathway)  
|Loss‑of‑function mutations or deletions → reduced de novo  DNA methylation; “epigenetic writer” defect (DNA methylation pathway)<ref name=":4">{{Cite journal|last=Zhang|first=Ping|last2=Zhang|first2=Mingzhi|date=2020-11-07|title=Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/33160401|journal=Clinical Epigenetics|volume=12|issue=1|pages=169|doi=10.1186/s13148-020-00962-x|issn=1868-7083|pmc=7648940|pmid=33160401}}</ref>
|Deregulation of gene silencing; tumour suppressor genes  may remain unmethylated or aberrantly methylated → genomic instability,  aberrant T‑cell differentiation/activation
|Deregulation of gene silencing; tumour suppressor genes  may remain unmethylated or aberrantly methylated → genomic instability,  aberrant T‑cell differentiation/activation
|-
|-
|TET2 (methylcytosine dioxygenase)
|TET2 (methylcytosine dioxygenase)
|Loss‑of‑function mutations → failure of DNA 5‑mC → 5‑hmC  demethylation (“epigenetic eraser” defect)  
|Loss‑of‑function mutations → failure of DNA 5‑mC → 5‑hmC  demethylation (“epigenetic eraser” defect)<ref name=":4" />
|Aberrant hypermethylation or demethylation patterns;  influences T‑cell development and malignant transformation (e.g., in T‑fh  lymphomas)
|Aberrant hypermethylation or demethylation patterns;  influences T‑cell development and malignant transformation (e.g., in T‑fh  lymphomas)
|-
|-
|IDH2 (metabolic enzyme altering epigenome)
|IDH2 (metabolic enzyme altering epigenome)
|Gain‑of‑function mutation (e.g., R172) → produces 2‑hydroxyglutarate  → inhibits TET family → epigenetic dysregulation  
|Gain‑of‑function mutation (e.g., R172) → produces 2‑hydroxyglutarate  → inhibits TET family → epigenetic dysregulation<ref name=":4" />
|Oncometabolite‑driven methylation changes, impaired  differentiation, proliferation of malignant T cells
|Oncometabolite‑driven methylation changes, impaired  differentiation, proliferation of malignant T cells
|-
|-
|ARID1A (SWI/SNF chromatin‑remodeller)
|ARID1A (SWI/SNF chromatin‑remodeller)
|Loss‑of‑function mutation/deletion → impaired nucleosome  remodelling, altered chromatin accessibility (“chromatin remodeller”)  
|Loss‑of‑function mutation/deletion → impaired nucleosome  remodelling, altered chromatin accessibility (“chromatin remodeller”)<ref name=":4" />
|Reduced tumour‑suppressor gene expression due to  chromatin compaction; may influence immune microenvironment and genomic  instability
|Reduced tumour‑suppressor gene expression due to  chromatin compaction; may influence immune microenvironment and genomic  instability
|-
|-
|KMT2D / KMT2A (H3K4 methyltransferases)
|KMT2D / KMT2A (H3K4 methyltransferases)
|Loss‑of‑function mutations (“histone‑writer” defect) →  decreased H3K4 methylation (activating mark)  
|Loss‑of‑function mutations (“histone‑writer” defect) →  decreased H3K4 methylation (activating mark)<ref name=":5">{{Cite journal|last=Ahmed|first=Nada|last2=Feldman|first2=Andrew L.|date=2020-02|title=Targeting epigenetic regulators in the treatment of T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/31903826|journal=Expert Review of Hematology|volume=13|issue=2|pages=127–139|doi=10.1080/17474086.2020.1711732|issn=1747-4094|pmc=7110907|pmid=31903826}}</ref>
|Impaired activation of gene expression programs  (differentiation, apoptosis) → contributes to malignant transformation
|Impaired activation of gene expression programs  (differentiation, apoptosis) → contributes to malignant transformation
|-
|-
|KDM6A (H3K27 demethylase)
|KDM6A (H3K27 demethylase)
|Loss‑of‑function → accumulation of H3K27me3 (repressive  histone mark) (“histone‑eraser” defect)  
|Loss‑of‑function → accumulation of H3K27me3 (repressive  histone mark) (“histone‑eraser” defect)<ref name=":5" />
|Further chromatin repression of tumour‑suppressor genes;  may enhance survival of malignant T cells
|Further chromatin repression of tumour‑suppressor genes;  may enhance survival of malignant T cells
|-
|-
|EZH2 (PRC2 complex methyltransferase)
|EZH2 (PRC2 complex methyltransferase)
|Overexpression/gain of function → increased H3K27me3  (“histone‑writer” overactivity) (PMC)
|Overexpression/gain of function → increased H3K27me3  (“histone‑writer” overactivity) <ref name=":4" />
|Enhanced silencing of differentiation/apoptosis genes;  contributes to aggressive lymphoma phenotypes
|Enhanced silencing of differentiation/apoptosis genes;  contributes to aggressive lymphoma phenotypes
|-
|-
|CREBBP / EP300 (histone acetyl‑transferases)
|CREBBP / EP300 (histone acetyl‑transferases)
|Loss‑of‑function mutations (“histone‑writer” defect) →  reduced histone acetylation and gene activation  
|Loss‑of‑function mutations (“histone‑writer” defect) →  reduced histone acetylation and gene activation<ref name=":5" />
|Diminished transcriptional activation of tumour‑suppressor/immune  genes; may drive malignant progression
|Diminished transcriptional activation of tumour‑suppressor/immune  genes; may drive malignant progression
|-
|-
|DNA methylation of specific tumour‑suppressor loci (e.g.,  CDKN2A promoter; FAS promoter)
|DNA methylation of specific tumour‑suppressor loci (e.g.,  CDKN2A promoter; FAS promoter)
|Hypermethylation of promoter CpG islands → silencing of tumor suppressor / apoptosis‑initiator genes  
|Hypermethylation of promoter CpG islands → silencing of tumor suppressor / apoptosis‑initiator genes<ref>{{Cite journal|last=Hara|first=Natsumi|last2=Sawada|first2=Yu|date=2022-03-24|title=Epigenetics of Cutaneous T-Cell Lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/35408897|journal=International Journal of Molecular Sciences|volume=23|issue=7|pages=3538|doi=10.3390/ijms23073538|issn=1422-0067|pmc=8998216|pmid=35408897}}</ref>
|Loss of cell‑cycle control or apoptosis leads to  malignant T‑cell survival/proliferation
|Loss of cell‑cycle control or apoptosis leads to  malignant T‑cell survival/proliferation
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
 
{| class="wikitable"
{| class="wikitable"
|'''Method'''
|'''Method'''
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There are currently '''no well-established familial or hereditary forms''' described in the literature.
There are currently '''no well-established familial or hereditary forms''' described in the literature.
==Additional Information==
==Additional Information==
NA
N/A
==Links==
==Links==


Put a link here or anywhere appropriate in this 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 wiki 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>
N/A


==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 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 />
==Notes==
<nowiki>*</nowiki>''Citation of this Page'': Azimpouran M, Kitahara S. “Primary cutaneous gamma/delta T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Primary_cutaneous_gamma/delta_T-cell_lymphoma</nowiki>.
 


==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 [[Leadership|''<u>Associate Editor</u>'']] 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.
<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|''<u>Associate Editor</u>'']] 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):   
Prior Author(s): N/A  
 
       
<nowiki>*</nowiki>''Citation of this Page'': “Primary cutaneous gamma/delta T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Primary_cutaneous_gamma/delta_T-cell_lymphoma</nowiki>.
[[Category:HAEM5]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:DISEASE]]
[[Category:Diseases P]]
[[Category:Diseases P]]
<references />
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