Compendium of Cancer Genome Aberrations

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

[unchecked revision][unchecked revision]
← Older editNewer edit →
VisualWikitext
Line 53: Line 53:
!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)'''
Line 157: Line 61:
|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)'''
Line 195: Line 99:
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|-
|1p
|9p
|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
|1p36.11
|18q (arm level; no precise minimal region specified)
|ARID1A
|Putative tumour suppressors (unspecified)
|P
|P
|No
|No
|Deleted in ~28% of cases. Indicates epigenetic/chromatin modifier pathway involvement<ref name=":0" />
|Recurrent deletion ~22% in PCGDTCL cohort. May reflect genomic instability and poor outcome<ref name=":0" />
|-
|-
|1q
|1q
Line 211: Line 123:
|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" />
|-
|-
|2q
|15q
|Loss
|Gain (arm‐level)
|2q37.3
|15q (approx chr15:30,000,000‑102,000,000)
|PDCD1
|Multiple genes on 15q (unspecified)
|P
|P
|No
|No
|Deletion in ~22% of cases. Immune checkpoint gene loss; potential therapeutic‑escape mechanism<ref name=":0" />
|Amplification in ~33% of cases. Likely reflects tumour evolution rather than diagnostic biomarker<ref name=":0" />
|-
|-
|7q
|7q
Line 227: Line 139:
|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.
|-
|-
|9p
|Focal deletion: CDKN2A
|Loss (deletion)
|Loss (homozygous/biallelic)
|9p21.3 (~ chr9:21,900,000‑22,200,000)
|within 9p21.3, CDKN2A region
|CDKN2A, CDKN2B
|CDKN2A
|P
|P
|No
|No
|High‐frequency  homozygous or biallelic deletion (~61% of cases; 45% biallelic) in PCGDTCL. (PMC)  Suggests aggressive biology, prognostic marker candidate<ref name=":0" />
|From GISTIC analysis: CDKN2A deletion in 61% of samples,  45% biallelic.  Key focal region in PCGDTCL<ref name=":0" />
|-
|-
|10q
|Focal deletion: ARID1A
|Loss
|Loss
|10q24.1
|unspecified (del/trunc)
|FAS
|ARID1A
|P
|P
|No
|No
|Deletion in ~22% of cases. Loss of apoptosis regulator; may contribute to immune‑escape<ref name=":0" />
|Deleted in ~28% of cases. Indicates epigenetic/chromatin modifier pathway involvement<ref name=":0" />
|-
|-
|15q
|Focal deletion: FAS
|Gain (arm‐level)
|Loss
|15q (approx chr15:30,000,000‑102,000,000)
|unspecified (biallelic)
|Multiple genes on 15q (unspecified)
|FAS
|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. Loss of apoptosis regulator; may contribute to immune‑escape<ref name=":0" />
|-
|-
|18q
|Focal deletion: PDCD1
|Loss
|Loss
|18q (arm level; no precise minimal region specified)
|unspecified
|Putative tumour suppressors (unspecified)
|PDCD1
|P
|P
|No
|No
|Recurrent deletion ~22% in PCGDTCL cohort. May reflect genomic instability and poor outcome<ref name=":0" />
|Deletion in ~22% of cases. Immune checkpoint gene loss; potential therapeutic‑escape mechanism<ref name=":0" />
|}
|}
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
Line 336: Line 248:
|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'''
Retrieved from "https://test.ccga.io/index.php/HAEM5:Primary_cutaneous_gamma/delta_T-cell_lymphoma"