HAEM5:Primary cutaneous gamma/delta T-cell lymphoma: Difference between revisions
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|P | |P | ||
|No | |No | ||
|High‐frequency homozygous or biallelic deletion (~61% of cases; 45% biallelic) in PCGDTCL. (PMC) Suggests aggressive biology, prognostic marker candidate | |High‐frequency homozygous or biallelic deletion (~61% of cases; 45% biallelic) in PCGDTCL. (PMC) Suggests aggressive biology, prognostic marker candidate<ref name=":0" /> | ||
|- | |- | ||
|18q | |18q | ||
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|P | |P | ||
|No | |No | ||
|Recurrent deletion ~22% in PCGDTCL cohort. | |Recurrent deletion ~22% in PCGDTCL cohort. May reflect genomic instability and poor outcome<ref name=":0" /> | ||
|- | |- | ||
|1q | |1q | ||
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|P / T | |P / T | ||
|No | |No | ||
|Amplification in ~33% of cases. | |Amplification in ~33% of cases. Potential gene dosage effect; specific driver gene not yet defined<ref name=":0" /> | ||
|- | |- | ||
|15q | |15q | ||
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|P | |P | ||
|No | |No | ||
|Amplification in ~33% of cases. | |Amplification in ~33% of cases. Likely reflects tumour evolution rather than diagnostic biomarker<ref name=":0" /> | ||
|- | |- | ||
|7q | |7q | ||
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|P | |P | ||
|No | |No | ||
|Amplification in ~39% of cases. | |Amplification in ~39% of cases. Suggests MAPK/other pathway involvement but specific gene not yet defined. | ||
|- | |- | ||
|Focal deletion: CDKN2A | |Focal deletion: CDKN2A | ||
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|P | |P | ||
|No | |No | ||
|From GISTIC analysis: CDKN2A deletion in 61% of samples, 45% biallelic. | |From GISTIC analysis: CDKN2A deletion in 61% of samples, 45% biallelic. Key focal region in PCGDTCL<ref name=":0" /> | ||
|- | |- | ||
|Focal deletion: ARID1A | |Focal deletion: ARID1A | ||
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|P | |P | ||
|No | |No | ||
|Deleted in ~28% of cases. | |Deleted in ~28% of cases. Indicates epigenetic/chromatin modifier pathway involvement<ref name=":0" /> | ||
|- | |- | ||
|Focal deletion: FAS | |Focal deletion: FAS | ||
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|P | |P | ||
|No | |No | ||
|Deletion in ~22% of cases. | |Deletion in ~22% of cases. Loss of apoptosis regulator; may contribute to immune‑escape<ref name=":0" /> | ||
|- | |- | ||
|Focal deletion: PDCD1 | |Focal deletion: PDCD1 | ||
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|P | |P | ||
|No | |No | ||
|Deletion in ~22% of cases. | |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== | ||
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!Clinical Relevance Details/Other Notes | !Clinical Relevance Details/Other Notes | ||
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|'''Arm‑level somatic copy‑number variation (SCNV)''' (average ~4 arm‑level events per case; median ~166.5 SCNVs per sample) | |'''Arm‑level somatic copy‑number variation (SCNV)''' (average ~4 arm‑level events per case; median ~166.5 SCNVs per sample)<ref name=":0" /> | ||
|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) | |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) | |'''Common''' (>20%) — nearly all cases show multiple arm‑level events (median 4 per sample) (PMC) | ||
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|High genomic complexity may explain aggressive behaviour and poor response to therapy. Could impact prognosis or treatment resistance but not yet in guidelines. | |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) | |'''High burden of somatic copy‑number variants (SCNVs) relative to single‐nucleotide variants (SNVs)''' (e.g., median ~166.5 SCNVs per sample) <ref name=":0" /> | ||
|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. | |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%) | |'''Common''' (>20%) | ||
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|Recognising this pattern may guide expectation of complexity, but this is not currently used clinically for diagnosis or treatment. | |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) | |'''Distinct cell‑of‑origin signature: Vδ1 vs Vδ2 subtype''' (epidermal/dermal Vδ1 vs panniculitic Vδ2) <ref name=":0" /> | ||
|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) | |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)<ref name=":0" /> | ||
|'''Recurrent''' (5‑20%) — this pattern applies in a subset of cases defined by tissue involvement and TCR subtype. | |'''Recurrent''' (5‑20%) — this pattern applies in a subset of cases defined by tissue involvement and TCR subtype. | ||
|D / P | |D / P | ||
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|This dichotomy may help stratify patients clinically (Vδ2 subtype worse prognosis) but is not currently part of formal diagnostic or therapeutic guidelines. | |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''' | |'''Ultraviolet (UV) mutational signature in Vδ1 subtype''' <ref name=":0" /> | ||
|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. | |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. | |'''Recurrent''' (5‑20%) — seen in Vδ1 cases but not all. | ||
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|Could suggest etiology and may influence prognosis; though not yet used for therapy selection. | |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) | |'''Frequent deletions of 9p21.3 (CDKN2A region)''' (part of the SCNV pattern) <ref name=":0" /> | ||
|Loss of CDKN2A/p14^ARF leads to cell‑cycle deregulation, loss of tumour suppressor control: a hallmark of many aggressive lymphomas | |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) | |'''Common''' (>20%) (approx 61% of cases) (PubMed) | ||
|P | |P | ||
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|Among the most prevalent genomic events in PCGDTCL — potential prognostic marker though not yet guideline‑endorsed. | |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)''' | |'''Multiple gains of oncogenic arms (e.g., 1q, 7q, 15q) and corresponding losses (eg 18q)''' <ref name=":0" /> | ||
|Gains may increase dosage of oncogenes; losses may reduce tumour suppressor dosage—together contributing to malignant phenotype | |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) | |'''Recurrent''' (5‑20%) for specific arm‑level changes (e.g., 1q gain ~33%, 7q ~39%, 15q ~33%) (PubMed) | ||
|P | |P | ||
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|These arm‑level events indicate complexity; may correlate with poorer prognosis; not yet actionable in therapy. | |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) | |'''TCR chain repertoire restriction / non‑random Vγ or Vδ usage''' (eg Vγ3Vδ2 in panniculitic cases) <ref name=":0" /> | ||
|Suggests antigen‑driven or tissue‐resident γδ T‑cell proliferation; highlights non‑random selection of malignant clones | |Suggests antigen‑driven or tissue‐resident γδ T‑cell proliferation; highlights non‑random selection of malignant clones | ||
|'''Recurrent''' (5‑20%) in defined subtypes | |'''Recurrent''' (5‑20%) in defined subtypes | ||
|D | |D | ||
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|Activating missense (e.g., p.N642H) → constitutive downstream STAT5 signalling | |Activating missense (e.g., p.N642H) → constitutive downstream STAT5 signalling | ||
|Oncogene | |Oncogene | ||
|Recurrent (~5‑20 %) — e.g., in the 2020 genomic study: JAK/STAT mutations ~21 % of cases | |Recurrent (~5‑20 %) — e.g., in the 2020 genomic study: JAK/STAT mutations ~21 % of cases<ref name=":0" /> | ||
|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 | ||
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[[Category:DISEASE]] | [[Category:DISEASE]] | ||
[[Category:Diseases P]] | [[Category:Diseases P]] | ||
<references /> | |||