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

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

==Primary Author(s)*==

Mahzad Azimpouran, MD; Sumire Kitahara, MD; Cedars-Sinai, Los Angeles, CA

{| class="wikitable"

|Acceptable

|N/A

==Gene Rearrangements==

{| class="wikitable sortable"

|-

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

!Clinical Relevance Details/Other Notes

|-

|'''Arm‑level chromosomal alterations (e.g., 9p,  18q deletions; 1q, 7q,15q gains)'''

|Copy number loss or gain → altered gene dosage of tumour  suppressors/oncogenes

|Other / chromosomal alteration

|D / P

|No

|-

|'''Fusion: FYN :: (probable partner TRAF3IP2)'''

|TRAF3IP2

|Oncogene / Other

|Rare (<5%) (single case reported)

|Fusion → juxtaposition of dimerization domain of PCM1  with kinase domain of JAK2 → constitutive JAK2 activation

|Oncogene

|T

|No

|Fusion → truncation/overexpression of ΔNp63 form →  oncogenic p63 signalling

|Oncogene / Other

|P / T

|No

|}

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

{| class="wikitable sortable"

|-

!Clinical Relevance Details/Other Notes

|-

|Loss

|P

|No

|-

|1q

|P / T

|No

|-

|P

|No

|-

|7q

|P

|No

|-

|P

|No

|-

|Loss

|P

|No

|-

|P

|No

|-

|Loss

|P

|No

|}

==Characteristic Chromosomal or Other Global Mutational Patterns==

{| class="wikitable sortable"

|-

!Clinical Relevance Details/Other Notes

|-

|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)

|High genomic complexity may explain aggressive behaviour  and poor response to therapy. Could impact prognosis or treatment resistance  but not yet in guidelines.

|-

|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%)

|Recognising this pattern may guide expectation of  complexity, but this is not currently used clinically for diagnosis or  treatment.

|-

|'''Recurrent''' (5‑20%) — this  pattern applies in a subset of cases defined by tissue involvement and TCR  subtype.

|D / P

|This dichotomy may help stratify patients clinically (Vδ2  subtype worse prognosis) but is not currently part of formal diagnostic or  therapeutic guidelines.

|-

|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.

|Could suggest etiology and may influence prognosis;  though not yet used for therapy selection.

|-

|P

|No

|Among the most prevalent genomic events in PCGDTCL —  potential prognostic marker though not yet guideline‑endorsed.

|-

|P

|No

|These arm‑level events indicate complexity; may correlate  with poorer prognosis; not yet actionable in therapy.

|-

|'''Recurrent''' (5‑20%) in defined  subtypes

|D

|}

==Gene Mutations (SNV/INDEL)==

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|-

|Activating missense (e.g., p.N642H) → constitutive  downstream STAT5 signalling

|Oncogene

|T / P: Therapeutic potential (JAK/STAT inhibition);  Prognostic implication (pathway addiction/resistance)

|No

|-

|'''STAT3'''

|Activating missense (SH2 domain) → constitutive STAT3  signalling

|Oncogene

|T / P

|No

|-

|'''JAK3'''

|Activating mutation (e.g., p.R657W) → JAK3 tyrosine  kinase activation

|Oncogene

|T

|No

|-

|'''KRAS'''

|Activating hotspot mutations (e.g., G12D, Q61H, D119N) →  RAS/MAPK activation

|Oncogene

|T / P

|No

|-

|'''NRAS'''

|Activating hotspot mutation → RAS/MAPK activation

|Oncogene

|T / P

|No

|Activating mutation → MAPK1 signalling activation

|Oncogene

|T

|No

|-

|'''MYC'''

|Activating missense mutation (e.g., p.P74L) → MYC pathway  up‑regulation

|Oncogene

|P / T

|No

|-

|'''MYCN'''

|Activating mutation (e.g., p.G34R) → MYCN pathway  activation

|Oncogene

|P / T

|No

|}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==

==Genes and Main Pathways Involved==

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|-

|-

|DNMT3A (DNA methyltransferase)

|Deregulation of gene silencing; tumour suppressor genes  may remain unmethylated or aberrantly methylated → genomic instability,  aberrant T‑cell differentiation/activation

|-

|TET2 (methylcytosine dioxygenase)

|Aberrant hypermethylation or demethylation patterns;  influences T‑cell development and malignant transformation (e.g., in T‑fh  lymphomas)

|-

|IDH2 (metabolic enzyme altering epigenome)

|Oncometabolite‑driven methylation changes, impaired  differentiation, proliferation of malignant T cells

|-

|ARID1A (SWI/SNF chromatin‑remodeller)

|Reduced tumour‑suppressor gene expression due to  chromatin compaction; may influence immune microenvironment and genomic  instability

|-

|KMT2D / KMT2A (H3K4 methyltransferases)

|Impaired activation of gene expression programs  (differentiation, apoptosis) → contributes to malignant transformation

|-

|KDM6A (H3K27 demethylase)

|Further chromatin repression of tumour‑suppressor genes;  may enhance survival of malignant T cells

|-

|EZH2 (PRC2 complex methyltransferase)

|Enhanced silencing of differentiation/apoptosis genes;  contributes to aggressive lymphoma phenotypes

|-

|CREBBP / EP300 (histone acetyl‑transferases)

|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)

|Loss of cell‑cycle control or apoptosis leads to  malignant T‑cell survival/proliferation

|}

==Genetic Diagnostic Testing Methods==

{| class="wikitable"

|'''Method'''

There are currently '''no well-established familial or hereditary forms''' described in the literature.

==Additional Information==

==Links==

==References==

<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.

[[Category:HAEM5]]

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