Compendium of Cancer Genome Aberrations

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

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|'''Genetic Alteration & Molecular  Pathogenesis'''
|'''Genetic Alteration & Molecular  Pathogenesis'''
|'''Tumour Suppressor / Oncogene / Other'''
|'''Tumour Suppressor / Oncogene / Other'''
|'''Prevalence*'''
|'''Prevalence (common>20%, recurrent 5-20% or rare <5%)'''
|'''D / P / T'''
|'''D / P / T'''
|'''Established clinical significance per guidelines?'''
|'''Established clinical significance per guidelines?'''
|'''Clinical relevance / Other notes'''
|'''Clinical relevance / Other notes'''
|'''Reference (PubMed)'''
|-
|-
|'''CDKN2A'''
|'''CDKN2A'''
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|No
|No
|High‐frequency  deletion, suggests aggressive biology and may be a prognostic marker
|High‐frequency  deletion, suggests aggressive biology and may be a prognostic marker
|<nowiki>PMID 32286303</nowiki> (PMC)
|-
|-
|'''ARID1A'''
|'''ARID1A'''
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|No
|No
|Indicates involvement of epigenetic/chromatin pathways in  PCGDTCL
|Indicates involvement of epigenetic/chromatin pathways in  PCGDTCL
|<nowiki>PMID 32286303</nowiki> (PMC)
|-
|-
|'''FAS'''
|'''FAS'''
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|No
|No
|Loss of FAS may contribute to immune‐escape of malignant γδ T‑cells
|Loss of FAS may contribute to immune‐escape of malignant γδ T‑cells
|<nowiki>PMID 32286303</nowiki> (PMC)
|-
|-
|'''PDCD1'''
|'''PDCD1'''
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|No
|No
|Suggests immune‐escape  mechanism; potential implications for checkpoint therapy though unproven
|Suggests immune‐escape  mechanism; potential implications for checkpoint therapy though unproven
|<nowiki>PMID 32286303</nowiki> (PMC)
|-
|-
|'''STAT5B'''
|'''STAT5B'''
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|No
|No
|JAK/STAT pathway dependency; early data suggest JAK‐inhibitor sensitivity in  analogous T‑cell neoplasms; investigational in PCGDTCL
|JAK/STAT pathway dependency; early data suggest JAK‐inhibitor sensitivity in  analogous T‑cell neoplasms; investigational in PCGDTCL
|<nowiki>PMID 25586472</nowiki> (PubMed)
|-
|-
|'''STAT3'''
|'''STAT3'''
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|No
|No
|Part of JAK/STAT alterations; less frequent than STAT5B  in PCGDTCL
|Part of JAK/STAT alterations; less frequent than STAT5B  in PCGDTCL
|<nowiki>PMID 25586472</nowiki> (PubMed)
|-
|-
|'''JAK3'''
|'''JAK3'''
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|No
|No
|Supports JAK/STAT pathway involvement; therapeutic  relevance remains investigational in this disease
|Supports JAK/STAT pathway involvement; therapeutic  relevance remains investigational in this disease
|<nowiki>PMID 32286303</nowiki> (PMC)
|-
|-
|'''KRAS'''
|'''KRAS'''
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|No
|No
|MAPK pathway potentially targetable; mutations associated  with poorer outcome in the cohort studied
|MAPK pathway potentially targetable; mutations associated  with poorer outcome in the cohort studied
|<nowiki>PMID 32286303</nowiki> (PMC)
|-
|-
|'''NRAS'''
|'''NRAS'''
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|No
|No
|Part of same pathway as KRAS though less common
|Part of same pathway as KRAS though less common
|<nowiki>PMID 32286303</nowiki> (PMC)
|-
|-
|'''MYC'''
|'''MYC'''
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|No
|No
|MYC pathway involvement may contribute to more aggressive  phenotype; direct targeting not yet established
|MYC pathway involvement may contribute to more aggressive  phenotype; direct targeting not yet established
|<nowiki>PMID 32286303</nowiki> (PMC)
|-
|-
|'''MYCN'''
|'''MYCN'''
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|No
|No
|Highlights involvement of MYC family beyond MYC itself in  PCGDTCL
|Highlights involvement of MYC family beyond MYC itself in  PCGDTCL
|<nowiki>PMID 32286303</nowiki> (PMC)
|-
|-
|'''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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|No
|No
|These structural changes suggest genomic instability and  aggressive biology; may help risk stratification though not diagnostic per se
|These structural changes suggest genomic instability and  aggressive biology; may help risk stratification though not diagnostic per se
|<nowiki>PMID 32286303</nowiki> (PMC)
|-
|-
|'''Fusion: FYN :: (probable partner TRAF3IP2)'''
|'''Fusion: FYN :: (probable partner TRAF3IP2)'''
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|No
|No
|Very recently described; may represent novel  driver/target; further cases needed
|Very recently described; may represent novel  driver/target; further cases needed
|<nowiki>PMID 39412302</nowiki> (PubMed)
|-
|-
|'''Fusion: PCM1 :: JAK2'''
|'''Fusion: PCM1 :: JAK2'''
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|No
|No
|Known in other T‑cell and myeloid neoplasms; in PCGDTCL  this double‐hit  case had PCM1::JAK2 + TBL1XR1::TP63 fusion; patient refractory to JAK  inhibitor
|Known in other T‑cell and myeloid neoplasms; in PCGDTCL  this double‐hit  case had PCM1::JAK2 + TBL1XR1::TP63 fusion; patient refractory to JAK  inhibitor
|<nowiki>PMID 37308177</nowiki> (PubMed)
|-
|-
|'''Fusion: TBL1XR1 :: TP63'''
|'''Fusion: TBL1XR1 :: TP63'''
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|No
|No
|Associated with aggressive behaviour in T‑cell lymphomas;  in the reported PCGDTCL case contributed to aggressive course and JAK  inhibitor resistance
|Associated with aggressive behaviour in T‑cell lymphomas;  in the reported PCGDTCL case contributed to aggressive course and JAK  inhibitor resistance
|<nowiki>PMID 37308177</nowiki> (PubMed)
|}
|}
{| class="wikitable sortable"
{| class="wikitable sortable"
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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>
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"
|'''Chr #'''
|'''Gain / Loss / Amp / LOH'''
|'''Minimal Region Cytoband and/or Approximate  Genomic Coordinates [Genome build GRCh38/hg38 if available]'''
|'''Relevant Gene(s)'''
|'''D / P / T (Diagnostic / Prognostic /  Therapeutic)'''
|'''Established clinical significance per  guidelines? (Yes/No; source)'''
|'''Clinical relevance / Notes'''
|-
|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.
|-
|18q
|Loss
|18q (arm level; no precise minimal region specified)
|Putative tumour suppressors (unspecified)
|P
|No
|Recurrent deletion ~22% in PCGDTCL cohort. (PMC)  May reflect genomic instability and poor outcome.
|-
|1q
|Gain (arm‐level  amplification)
|1q (approx chr1:144,000,000‑249,000,000)
|Multiple genes on 1q (unspecified)
|P / T
|No
|Amplification in ~33% of cases. (PMC)  Potential gene dosage effect; specific driver gene not yet defined.
|-
|15q
|Gain (arm‐level)
|15q (approx chr15:30,000,000‑102,000,000)
|Multiple genes on 15q (unspecified)
|P
|No
|Amplification in ~33% of cases. (PMC)  Likely reflects tumour evolution rather than diagnostic biomarker.
|-
|7q
|Gain (arm‐level)
|7q (approx chr7:100,000,000‑159,000,000)
|Multiple genes on 7q (unspecified)
|P
|No
|Amplification in ~39% of cases. (PMC)  Suggests MAPK/other pathway involvement but specific gene not yet defined.
|-
|Focal deletion: CDKN2A
|Loss (homozygous/biallelic)
|within 9p21.3, CDKN2A region
|CDKN2A
|P
|No
|From GISTIC analysis: CDKN2A deletion in 61% of samples,  45% biallelic. (PMC)  Key focal region in PCGDTCL.
|-
|Focal deletion: ARID1A
|Loss
|unspecified (del/trunc)
|ARID1A
|P
|No
|Deleted in ~28% of cases. (PMC)  Indicates epigenetic/chromatin modifier pathway involvement.
|-
|Focal deletion: FAS
|Loss
|unspecified (biallelic)
|FAS
|P
|No
|Deletion in ~22% of cases. (PMC)  Loss of apoptosis regulator; may contribute to immune‑escape.
|-
|Focal deletion: PDCD1
|Loss
|unspecified
|PDCD1
|P
|No
|Deletion in ~22% of cases. (PMC)  Immune checkpoint gene loss; potential therapeutic‑escape mechanism.
|}
{| class="wikitable sortable"
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|-
|-
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==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>
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"
|'''Chromosomal/Global Pattern'''
|'''Molecular Pathogenesis / Explanation'''
|'''Prevalence (common>20%, recurrent 5-20% or rare <5%)'''
|'''D / P / T'''
|'''Established Clinical Significance per  Guidelines? (Yes/No; Source)'''
|'''Clinical Relevance / Other Notes'''
|-
|'''Arm‑level somatic copy‑number variation  (SCNV)''' (average ~4 arm‑level events per case; median ~166.5  SCNVs per sample) (PMC)
|Reflects genomic instability; multiple gains and losses  of whole chromosome arms likely contribute to oncogenesis and progression by  altering gene dosage of multiple oncogenes/tumour suppressors simultaneously.  (PMC)
|'''Common''' (>20%) — nearly all  cases show multiple arm‑level events (median 4 per sample) (PMC)
|P
|No
|High genomic complexity may explain aggressive behaviour  and poor response to therapy. Could impact prognosis or treatment resistance  but not yet in guidelines.
|-
|'''High burden of somatic copy‑number variants  (SCNVs) relative to single‐nucleotide  variants (SNVs)''' (e.g., median ~166.5 SCNVs per sample) (PMC)
|Suggests that structural genomic alterations dominate the  mutational landscape, perhaps more so than classical hotspot SNVs, indicating  a biology driven by large‑scale genomic disruption rather than just point  mutations.
|'''Common''' (>20%)
|P
|No
|Recognising this pattern may guide expectation of  complexity, but this is not currently used clinically for diagnosis or  treatment.
|-
|'''Distinct cell‑of‑origin signature: Vδ1 vs Vδ2  subtype''' (epidermal/dermal Vδ1 vs panniculitic Vδ2) (PMC)
|Different tissue compartments (epidermis/dermis vs  subcutaneous) correspond to distinct γδ T‑cell subsets (Vδ1 vs Vδ2). The cell‑of‑origin  influences mutational signatures (eg UV signature in Vδ1) and clinical  phenotype (Vδ2 more aggressive). (PMC)
|'''Recurrent''' (5‑20%) — this  pattern applies in a subset of cases defined by tissue involvement and TCR  subtype.
|D / P
|No
|This dichotomy may help stratify patients clinically (Vδ2  subtype worse prognosis) but is not currently part of formal diagnostic or  therapeutic guidelines.
|-
|'''Ultraviolet (UV) mutational signature in Vδ1  subtype''' (PMC)
|The epidermal/dermal Vδ1 γδ T‑cell lymphomas exhibit a UV  signature in their mutation spectrum, likely reflecting skin localization and  UV exposure contributing to oncogenesis.
|'''Recurrent''' (5‑20%) — seen in  Vδ1 cases but not all.
|P
|No
|Could suggest etiology and may influence prognosis;  though not yet used for therapy selection.
|-
|'''Frequent deletions of 9p21.3 (CDKN2A region)'''  (part of the SCNV pattern) (PMC)
|Loss of CDKN2A/p14^ARF leads to cell‑cycle deregulation,  loss of tumour suppressor control: a hallmark of many aggressive lymphomas.
|'''Common''' (>20%) (approx 61% of  cases) (PubMed)
|P
|No
|Among the most prevalent genomic events in PCGDTCL —  potential prognostic marker though not yet guideline‑endorsed.
|-
|'''Multiple gains of oncogenic arms (e.g., 1q,  7q, 15q) and corresponding losses (eg 18q)''' (PMC)
|Gains may increase dosage of oncogenes; losses may reduce  tumour suppressor dosage—together contributing to malignant phenotype.
|'''Recurrent''' (5‑20%) for specific  arm‑level changes (e.g., 1q gain ~33%, 7q ~39%, 15q ~33%) (PubMed)
|P
|No
|These arm‑level events indicate complexity; may correlate  with poorer prognosis; not yet actionable in therapy.
|-
|'''TCR chain repertoire restriction / non‑random  Vγ or Vδ usage''' (eg Vγ3Vδ2 in panniculitic cases) (PMC)
|Suggests antigen‑driven or tissue‐resident γδ T‑cell  proliferation; highlights non‑random selection of malignant clones.
|'''Recurrent''' (5‑20%) in defined  subtypes
|D
|No
|Might help refine subclassification of PCGDTCL; not  currently used in routine diagnostic algorithms.
|}
{| class="wikitable sortable"
{| 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>
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"
|'''Gene'''
|'''Genetic Alteration (SNV/INDEL) + presumed  mechanism'''
|'''Tumour Suppressor / Oncogene / Other'''
|'''Prevalence in PCGDTCL*'''
|'''D / P / T (Diagnostic / Prognostic /  Therapeutic)'''
|'''Established Clinical Significance per  Guidelines?'''
|'''Clinical Relevance / Other Notes'''
|-
|'''STAT5B'''
|Activating missense (e.g., p.N642H) → constitutive  downstream STAT5 signalling
|Oncogene
|Recurrent (~5‑20 %) — e.g., in the 2020 genomic study:  JAK/STAT mutations ~21 % of cases. (PMC)
|T / P: Therapeutic potential (JAK/STAT inhibition);  Prognostic implication (pathway addiction/resistance)
|No
|Mutant STAT5B (especially N642H) shown to induce T‑cell  neoplasia in models; in PCGDTCL JAK/STAT addiction shown clinically  (JCI 2025) (Ovid)
|-
|'''STAT3'''
|Activating missense (SH2 domain) → constitutive STAT3  signalling
|Oncogene
|Rare (<5 %) to Recurrent (≈5‑10 %) (in NK/γδ‑T  lymphomas earlier) (PubMed)
|T / P
|No
|Less frequent than STAT5B in PCGDTCL; part of JAK/STAT  pathway involvement.
|-
|'''JAK3'''
|Activating mutation (e.g., p.R657W) → JAK3 tyrosine  kinase activation
|Oncogene
|Rare (<5 %) (noted in the Daniels et al. cohort) (PMC)
|T
|No
|Supports JAK/STAT involvement; one case report showed  response to JAK inhibition. (JCI)
|-
|'''KRAS'''
|Activating hotspot mutations (e.g., G12D, Q61H, D119N) →  RAS/MAPK activation
|Oncogene
|Recurrent (~5‑20 %) — “KRAS was the most frequently  mutated oncogene” in Daniels et al. (PMC)
|T / P
|No
|MAPK pathway appears relevant; patients with MAPK‑pathway  driver mutations had worse survival in the cohort. (PubMed)
|-
|'''NRAS'''
|Activating hotspot mutation → RAS/MAPK activation
|Oncogene
|Rare (<5 %) to Recurrent (~5‑10 %) (PMC)
|T / P
|No
|Part of the same RAS/MAPK pathway as KRAS; less common.
|-
|'''MAPK1'''
|Activating mutation → MAPK1 signalling activation
|Oncogene
|Rare (<5 %) (PMC)
|T
|No
|Also in MAPK pathway; limited data in PCGDTCL.
|-
|'''MYC'''
|Activating missense mutation (e.g., p.P74L) → MYC pathway  up‑regulation
|Oncogene
|Rare (<5 %) (PMC)
|P / T
|No
|MYC pathway involvement may contribute to the aggressive  phenotype; direct targeting not yet established.
|-
|'''MYCN'''
|Activating mutation (e.g., p.G34R) → MYCN pathway  activation
|Oncogene
|Rare (<5 %) (PMC)
|P / T
|No
|Highlights involvement of MYC‑family beyond MYC itself in  this disease.
|}
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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==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>
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"
|'''Gene'''
|'''Alteration / Pathway'''
|'''Pathophysiologic Outcome'''
|-
|DNMT3A (DNA methyltransferase)
|Loss‑of‑function mutations or deletions → reduced de novo  DNA methylation; “epigenetic writer” defect (DNA methylation pathway) (BioMed  Central)
|Deregulation of gene silencing; tumour suppressor genes  may remain unmethylated or aberrantly methylated → genomic instability,  aberrant T‑cell differentiation/activation
|-
|TET2 (methylcytosine dioxygenase)
|Loss‑of‑function mutations → failure of DNA 5‑mC → 5‑hmC  demethylation (“epigenetic eraser” defect) (BioMed  Central)
|Aberrant hypermethylation or demethylation patterns;  influences T‑cell development and malignant transformation (e.g., in T‑fh  lymphomas)
|-
|IDH2 (metabolic enzyme altering epigenome)
|Gain‑of‑function mutation (e.g., R172) → produces 2‑hydroxyglutarate  → inhibits TET family → epigenetic dysregulation (BioMed  Central)
|Oncometabolite‑driven methylation changes, impaired  differentiation, proliferation of malignant T cells
|-
|ARID1A (SWI/SNF chromatin‑remodeller)
|Loss‑of‑function mutation/deletion → impaired nucleosome  remodelling, altered chromatin accessibility (“chromatin remodeller”) (PMC)
|Reduced tumour‑suppressor gene expression due to  chromatin compaction; may influence immune microenvironment and genomic  instability
|-
|KMT2D / KMT2A (H3K4 methyltransferases)
|Loss‑of‑function mutations (“histone‑writer” defect) →  decreased H3K4 methylation (activating mark) (PMC)
|Impaired activation of gene expression programs  (differentiation, apoptosis) → contributes to malignant transformation
|-
|KDM6A (H3K27 demethylase)
|Loss‑of‑function → accumulation of H3K27me3 (repressive  histone mark) (“histone‑eraser” defect) (PMC)
|Further chromatin repression of tumour‑suppressor genes;  may enhance survival of malignant T cells
|-
|EZH2 (PRC2 complex methyltransferase)
|Overexpression/gain of function → increased H3K27me3  (“histone‑writer” overactivity) (PMC)
|Enhanced silencing of differentiation/apoptosis genes;  contributes to aggressive lymphoma phenotypes
|-
|CREBBP / EP300 (histone acetyl‑transferases)
|Loss‑of‑function mutations (“histone‑writer” defect) →  reduced histone acetylation and gene activation (PMC)
|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)
|Hypermethylation of promoter CpG islands → silencing of  tumour suppressor / apoptosis‑initiator genes (PMC)
|Loss of cell‑cycle control or apoptosis leads to  malignant T‑cell survival/proliferation
|}
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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==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>
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span>
{| class="wikitable"
|'''Method'''
|'''Description'''
|'''Type of Alteration Detected'''
|'''Advantages'''
|'''Limitations'''
|'''Clinical Use in PCGDTCL'''
|-
|'''Next-Generation Sequencing (NGS)'''
|High-throughput sequencing of targeted gene panels,  whole-exome, or whole-genome sequencing
|SNVs, INDELs, copy number variants (CNVs), some fusions  (if RNA-seq included)
|Comprehensive mutation detection; scalable; can detect  multiple variants simultaneously
|Requires high-quality DNA/RNA; bioinformatics expertise  needed; cost-intensive
|Main tool for mutational profiling in PCGDTCL; used in  research and increasingly in clinical labs
|-
|'''Targeted Gene Panels (amplicon or hybrid  capture-based)'''
|Sequencing of a defined set of genes known to be relevant
|SNVs, INDELs, limited CNVs, hotspot fusions (if included)
|Faster, cheaper than WES/WGS; focused on clinically  relevant genes
|May miss novel or unexpected mutations; limited to panel  content
|Often used clinically to screen for mutations in  JAK/STAT, RAS pathways in PCGDTCL
|-
|'''Fluorescence In Situ Hybridization (FISH)'''
|DNA probes hybridize to metaphase or interphase  chromosomes
|Structural chromosomal alterations, gene fusions,  amplifications, deletions
|Visualizes gene rearrangements and copy number changes;  established clinical use
|Limited to known targets; low resolution; labor-intensive
|Used to detect known translocations or gene  amplifications (e.g., MYC) in lymphoma diagnosis
|-
|'''Array Comparative Genomic Hybridization  (aCGH) / SNP Arrays'''
|Genome-wide detection of copy number alterations and LOH
|Copy number gains, losses, LOH (Loss of heterozygosity)
|Genome-wide coverage; detects submicroscopic CNVs
|Cannot detect balanced translocations or point mutations;  resolution depends on array density
|Useful for detecting large chromosomal alterations in  lymphoma samples
|-
|'''RNA Sequencing (RNA-Seq)'''
|Sequencing of transcriptome
|Gene fusions, splice variants, expression levels
|Detects novel and known fusions; measures gene  expression; alternative splicing
|RNA quality sensitive; bioinformatics expertise needed
|Research use for identifying novel fusion partners or  expression signatures in PCGDTCL
|-
|'''Sanger Sequencing'''
|Chain termination sequencing of PCR-amplified regions
|SNVs and small indels
|Gold standard for validation; high accuracy
|Low throughput; not suitable for large panels
|Used to confirm NGS-identified mutations
|-
|'''Digital Droplet PCR (ddPCR) / qPCR'''
|Highly sensitive quantification of known mutations or  gene rearrangements
|Known point mutations, copy number changes
|Very sensitive, quantitative; fast turnaround
|Limited to known mutations; not comprehensive
|Useful for monitoring known mutations (e.g., STAT5B  N642H) in minimal residual disease (MRD) or treatment response
|-
|'''Immunohistochemistry (IHC)'''  (surrogate genetic marker)
|Antibody staining of protein expression
|Protein expression reflecting genetic alterations (e.g.,  pSTAT5B, MYC)
|Widely available; easy to implement
|Indirect; may not perfectly correlate with mutation  status
|Supportive role in diagnosis and prognosis, not  definitive genetic test
|}
==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>
There are currently '''no well-established familial or hereditary forms''' described in the literature.
==Additional Information==
==Additional Information==
Put your text here
Put your text here
Retrieved from "https://test.ccga.io/index.php/HAEM5:Primary_cutaneous_gamma/delta_T-cell_lymphoma"