HAEM5:Primary cutaneous gamma/delta T-cell lymphoma - Revision history

Sumire.Kitahara: /* Gene Rearrangements */

2026-01-07T03:48:12Z

Gene Rearrangements

← Older revision		Revision as of 22:48, 6 January 2026
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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)*==
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	==Gene Rearrangements==		==Gene Rearrangements==

	{\| 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>
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
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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>
	{\| 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>
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
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	\|}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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	\|}		\|}
	==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 />~~

Sumire.Kitahara: /* Individual Region Genomic Gain/Loss/LOH */

2026-01-07T03:21:33Z

Individual Region Genomic Gain/Loss/LOH

← Older revision		Revision as of 22:21, 6 January 2026
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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: ARID1A~~		\|9p
	\|Loss		\|Loss (deletion)
	\|~~unspecified~~ (~~del/trunc~~)		\|9p21.3 (~ chr9:21,900,000‑22,200,000)
	\|~~ARID1A~~		\|CDKN2A, CDKN2B
	\|P		\|P
	\|No		\|No
	\|~~Deleted in~~ ~28% of cases. ~~Indicates epigenetic/chromatin modifier pathway involvement~~<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: FAS~~		\|10q
	\|Loss		\|Loss
	\|~~unspecified (biallelic)~~		\|10q24.1
	\|FAS		\|FAS
	\|P		\|P
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	\|Deletion in ~22% of cases. Loss of apoptosis regulator; may contribute to immune‑escape<ref name=":0" />		\|Deletion in ~22% of cases. Loss of apoptosis regulator; may contribute to immune‑escape<ref name=":0" />
	\|-		\|-
	\|~~Focal deletion~~: ~~PDCD1~~		\|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. Likely reflects tumour evolution rather than diagnostic biomarker<ref name=":0" />
			\|-
			\|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==

Sumire.Kitahara: /* Gene Rearrangements */

2026-01-07T03:17:21Z

Gene Rearrangements

← Older revision		Revision as of 22:17, 6 January 2026
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	==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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	{\| class="wikitable"		{\| class="wikitable"
	\|+
	\|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"		{\| class="wikitable sortable"
	\|-		\|-
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	\|No		\|No
	\|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~~
	~~\|Loss (homozygous/biallelic)~~
	~~\|within 9p21.3, CDKN2A region~~
	~~\|CDKN2A~~
	\|P
	~~\|No~~
	~~\|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

Sumire.Kitahara: /* Gene Rearrangements */

2026-01-07T03:14:45Z

Gene Rearrangements

Show changes

Sumire.Kitahara: /* Gene Mutations (SNV/INDEL) */

2026-01-07T03:14:19Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 22:14, 6 January 2026
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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==
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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" /><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'''

Mahzad.Azimpouran at 20:51, 7 November 2025

2025-11-07T20:51:54Z

Mahzad.Azimpouran at 20:42, 7 November 2025

2025-11-07T20:42:42Z

← Older revision		Revision as of 15:42, 7 November 2025
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	\|Activating missense (e.g., N642H) → constitutive STAT5B signalling (JAK/STAT pathway)		\|Activating missense (e.g., N642H) → constitutive STAT5B signalling (JAK/STAT pathway)
	\|Oncogene		\|Oncogene
	\|Recurrent (5‑20%) (JAK/STAT mutations ~21%~~) (PubMed~~)		\|Recurrent (5‑20%) (JAK/STAT mutations ~21%)
	\|T / P		\|T / P
	\|No		\|No
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	\|Activating missense → constitutive STAT3 signalling (JAK/STAT cascade)		\|Activating missense → constitutive STAT3 signalling (JAK/STAT cascade)
	\|Oncogene		\|Oncogene
	\|Rare (<5%) to Recurrent (~5‑20%~~) (PubMed~~)		\|Rare (<5%) to Recurrent (~5‑20%)
	\|T / P		\|T / P
	\|No		\|No
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	\|Activating mutation (e.g., R657W) → JAK3 tyrosine kinase activation (JAK/STAT pathway)		\|Activating mutation (e.g., R657W) → JAK3 tyrosine kinase activation (JAK/STAT pathway)
	\|Oncogene		\|Oncogene
	\|Rare (<5%~~) (PMC~~)		\|Rare (<5%)
	\|T		\|T
	\|No		\|No
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	\|Activating hotspot mutations (e.g., G12D, Q61H) → RAS/MAPK pathway activation		\|Activating hotspot mutations (e.g., G12D, Q61H) → RAS/MAPK pathway activation
	\|Oncogene		\|Oncogene
	\|Recurrent (5‑20%~~) (PubMed~~)		\|Recurrent (5‑20%)
	\|T / P		\|T / P
	\|No		\|No
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	\|Activating hotspot mutation → RAS/MAPK pathway activation		\|Activating hotspot mutation → RAS/MAPK pathway activation
	\|Oncogene		\|Oncogene
	\|Rare (<5%) to Recurrent (~5‑20%~~) (PMC~~)		\|Rare (<5%) to Recurrent (~5‑20%)
	\|T / P		\|T / P
	\|No		\|No
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	\|Activating missense mutation (e.g., P74L) → MYC pathway up‑regulation		\|Activating missense mutation (e.g., P74L) → MYC pathway up‑regulation
	\|Oncogene		\|Oncogene
	\|Rare (<5%~~) (PMC~~)		\|Rare (<5%)
	\|P / T		\|P / T
	\|No		\|No
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	\|Activating mutation (e.g., G34R) → MYCN pathway activation		\|Activating mutation (e.g., G34R) → MYCN pathway activation
	\|Oncogene		\|Oncogene
	\|Rare (<5%~~) (PMC~~)		\|Rare (<5%)
	\|P / T		\|P / T
	\|No		\|No
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	\|Copy number loss or gain → altered gene dosage of tumour suppressors/oncogenes		\|Copy number loss or gain → altered gene dosage of tumour suppressors/oncogenes
	\|Other / chromosomal alteration		\|Other / chromosomal alteration
	\|Recurrent (5‑20%) (9p del ~22%, 18q del ~22%; 1q/7q/15q gains ~33‑39%~~) (PMC~~)		\|Recurrent (5‑20%) (9p del ~22%, 18q del ~22%; 1q/7q/15q gains ~33‑39%)
	\|D / P		\|D / P
	\|No		\|No
Line 161:		Line 161:
	\|'''Fusion: FYN :: (probable partner TRAF3IP2)'''		\|'''Fusion: FYN :: (probable partner TRAF3IP2)'''
	\|TRAF3IP2		\|TRAF3IP2
	\|Structural alteration – deletion/exon8 deletion → (in other T‑cell lymphomas) FYN::TRAF3IP2 fusion leading to SRC‑family kinase activation; in this PCGDTCL case FYN exon8 deletion noted ~~(PubMed)~~		\|Structural alteration – deletion/exon8 deletion → (in other T‑cell lymphomas) FYN::TRAF3IP2 fusion leading to SRC‑family kinase activation; in this PCGDTCL case FYN exon8 deletion noted
	\|Oncogene / Other		\|Oncogene / Other
	\|Rare (<5%) (single case reported)		\|Rare (<5%) (single case reported)
Line 172:		Line 172:
	\|Fusion → juxtaposition of dimerization domain of PCM1 with kinase domain of JAK2 → constitutive JAK2 activation		\|Fusion → juxtaposition of dimerization domain of PCM1 with kinase domain of JAK2 → constitutive JAK2 activation
	\|Oncogene		\|Oncogene
	\|Rare (<5%) (single documented PCGDTCL case~~) (PubMed~~)		\|Rare (<5%) (single documented PCGDTCL case)
	\|T		\|T
	\|No		\|No
Line 181:		Line 181:
	\|Fusion → truncation/overexpression of ΔNp63 form → oncogenic p63 signalling		\|Fusion → truncation/overexpression of ΔNp63 form → oncogenic p63 signalling
	\|Oncogene / Other		\|Oncogene / Other
	\|Rare (<5%) (same single case) (~~PubMed)~~		\|Rare (<5%) (same single case) (
	\|P / T		\|P / T
	\|No		\|No
Line 309:		Line 309:
	\|'''Frequent deletions of 9p21.3 (CDKN2A region)''' (part of the SCNV pattern) <ref name=":0" />		\|'''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)
	\|P		\|P
	\|No		\|No
Line 316:		Line 316:
	\|'''Multiple gains of oncogenic arms (e.g., 1q, 7q, 15q) and corresponding losses (eg 18q)''' <ref name=":0" />		\|'''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%)
	\|P		\|P
	\|No		\|No
Line 344:		Line 344:
	\|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 ~~(JCI 2025) (Ovid)~~		\|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>
	\|-		\|-
	\|'''STAT3'''		\|'''STAT3'''
Line 352:		Line 352:
	\|T / P		\|T / P
	\|No		\|No
	\|Less frequent than STAT5B in PCGDTCL; part of JAK/STAT pathway involvement.		\|Less frequent than STAT5B in PCGDTCL; part of JAK/STAT pathway involvement<ref name=":0" /><ref name=":1" />
	\|-		\|-
	\|'''JAK3'''		\|'''JAK3'''
Line 360:		Line 360:
	\|T		\|T
	\|No		\|No
	\|Supports JAK/STAT involvement; one case report showed response to JAK inhibition~~. (JCI)~~		\|Supports JAK/STAT involvement; one case report showed response to JAK inhibition<ref name=":3" />
	\|-		\|-
	\|'''KRAS'''		\|'''KRAS'''
Line 368:		Line 368:
	\|T / P		\|T / P
	\|No		\|No
	\|MAPK pathway appears relevant; patients with MAPK‑pathway driver mutations had worse survival in the cohort~~. (PubMed)~~		\|MAPK pathway appears relevant; patients with MAPK‑pathway driver mutations had worse survival in the cohort<ref name=":0" />
	\|-		\|-
	\|'''NRAS'''		\|'''NRAS'''
Line 384:		Line 384:
	\|T		\|T
	\|No		\|No
	\|Also in MAPK pathway; limited data in PCGDTCL.		\|Also in MAPK pathway; limited data in PCGDTCL<ref name=":0" /><ref name=":1" />
	\|-		\|-
	\|'''MYC'''		\|'''MYC'''

Mahzad.Azimpouran at 19:58, 29 October 2025

2025-10-29T19:58:08Z

← Older revision		Revision as of 14:58, 29 October 2025
Line 349:		Line 349:
	\|Activating missense (SH2 domain) → constitutive STAT3 signalling		\|Activating missense (SH2 domain) → constitutive STAT3 signalling
	\|Oncogene		\|Oncogene
	\|Rare (<5 %) to Recurrent (≈5‑10 %) (in NK/γδ‑T lymphomas earlier~~) (PubMed~~)		\|Rare (<5 %) to Recurrent (≈5‑10 %) (in NK/γδ‑T lymphomas earlier)
	\|T / P		\|T / P
	\|No		\|No
Line 357:		Line 357:
	\|Activating mutation (e.g., p.R657W) → JAK3 tyrosine kinase activation		\|Activating mutation (e.g., p.R657W) → JAK3 tyrosine kinase activation
	\|Oncogene		\|Oncogene
	\|Rare (<5 %) (noted in the Daniels et al. cohort~~) (PMC~~)		\|Rare (<5 %) (noted in the Daniels et al. cohort)
	\|T		\|T
	\|No		\|No
Line 365:		Line 365:
	\|Activating hotspot mutations (e.g., G12D, Q61H, D119N) → RAS/MAPK activation		\|Activating hotspot mutations (e.g., G12D, Q61H, D119N) → RAS/MAPK activation
	\|Oncogene		\|Oncogene
	\|Recurrent (~5‑20 %) — “KRAS was the most frequently mutated oncogene” ~~in Daniels et al. (PMC)~~		\|Recurrent (~5‑20 %) — “KRAS was the most frequently mutated oncogene” <ref name=":0" />
	\|T / P		\|T / P
	\|No		\|No
Line 373:		Line 373:
	\|Activating hotspot mutation → RAS/MAPK activation		\|Activating hotspot mutation → RAS/MAPK activation
	\|Oncogene		\|Oncogene
	\|Rare (<5 %) to Recurrent (~5‑10 %~~) (PMC~~)		\|Rare (<5 %) to Recurrent (~5‑10 %)
	\|T / P		\|T / P
	\|No		\|No
Line 381:		Line 381:
	\|Activating mutation → MAPK1 signalling activation		\|Activating mutation → MAPK1 signalling activation
	\|Oncogene		\|Oncogene
	\|Rare (<5 %~~) (PMC~~)		\|Rare (<5 %)
	\|T		\|T
	\|No		\|No
Line 389:		Line 389:
	\|Activating missense mutation (e.g., p.P74L) → MYC pathway up‑regulation		\|Activating missense mutation (e.g., p.P74L) → MYC pathway up‑regulation
	\|Oncogene		\|Oncogene
	\|Rare (<5 %~~) (PMC~~)		\|Rare (<5 %)
	\|P / T		\|P / T
	\|No		\|No
Line 397:		Line 397:
	\|Activating mutation (e.g., p.G34R) → MYCN pathway activation		\|Activating mutation (e.g., p.G34R) → MYCN pathway activation
	\|Oncogene		\|Oncogene
	\|Rare (<5 %~~) (PMC~~)		\|Rare (<5 %)
	\|P / T		\|P / T
	\|No		\|No
Line 411:		Line 411:
	\|-		\|-
	\|DNMT3A (DNA methyltransferase)		\|DNMT3A (DNA methyltransferase)
	\|Loss‑of‑function mutations or deletions → reduced de novo DNA methylation; “epigenetic writer” defect (DNA methylation pathway~~) (BioMed Central~~)		\|Loss‑of‑function mutations or deletions → reduced de novo DNA methylation; “epigenetic writer” defect (DNA methylation pathway)
	\|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~~) (BioMed Central~~)		\|Loss‑of‑function mutations → failure of DNA 5‑mC → 5‑hmC demethylation (“epigenetic eraser” defect)
	\|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 ~~(BioMed Central)~~		\|Gain‑of‑function mutation (e.g., R172) → produces 2‑hydroxyglutarate → inhibits TET family → epigenetic dysregulation
	\|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”~~) (PMC~~)		\|Loss‑of‑function mutation/deletion → impaired nucleosome remodelling, altered chromatin accessibility (“chromatin remodeller”)
	\|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~~) (PMC~~)		\|Loss‑of‑function mutations (“histone‑writer” defect) → decreased H3K4 methylation (activating mark)
	\|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~~) (PMC~~)		\|Loss‑of‑function → accumulation of H3K27me3 (repressive histone mark) (“histone‑eraser” defect)
	\|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
	\|-		\|-
Line 439:		Line 439:
	\|-		\|-
	\|CREBBP / EP300 (histone acetyl‑transferases)		\|CREBBP / EP300 (histone acetyl‑transferases)
	\|Loss‑of‑function mutations (“histone‑writer” defect) → reduced histone acetylation and gene activation ~~(PMC)~~		\|Loss‑of‑function mutations (“histone‑writer” defect) → reduced histone acetylation and gene activation
	\|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 ~~tumour~~ suppressor / apoptosis‑initiator genes ~~(PMC)~~		\|Hypermethylation of promoter CpG islands → silencing of tumor suppressor / apoptosis‑initiator genes
	\|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
	\|}		\|}

Mahzad.Azimpouran at 19:55, 29 October 2025

2025-10-29T19:55:44Z

Show changes

Mahzad.Azimpouran at 19:38, 29 October 2025

2025-10-29T19:38:36Z

← Older revision		Revision as of 14:38, 29 October 2025
Line 55:		Line 55:
	\|-		\|-
	\|'''CDKN2A'''\|\|—\|\|Homozygous or biallelic deletion → loss of p16^INK4A/p14^ARF function (cell‑cycle control)\|\|Tumour suppressor		\|'''CDKN2A'''\|\|—\|\|Homozygous or biallelic deletion → loss of p16^INK4A/p14^ARF function (cell‑cycle control)\|\|Tumour suppressor
	\|'''Common''' (>20%) (~61% in cohort) ~~(PubMed)~~		\|'''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		\|P
	\|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<ref name=":0" />
	\|-		\|-
	\|'''ARID1A'''		\|'''ARID1A'''
Line 67:		Line 67:
	\|Other / P		\|Other / P
	\|No		\|No
	\|Indicates involvement of epigenetic/chromatin pathways in PCGDTCL		\|Indicates involvement of epigenetic/chromatin pathways in PCGDTCL<ref name=":0" />
	\|-		\|-
	\|'''FAS'''		\|'''FAS'''
Line 76:		Line 76:
	\|Other / P		\|Other / P
	\|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<ref name=":0" />
	\|-		\|-
	\|'''PDCD1'''		\|'''PDCD1'''
Line 85:		Line 85:
	\|Other / P		\|Other / P
	\|No		\|No
	\|Suggests immune‐escape mechanism; potential implications for checkpoint therapy though unproven		\|Suggests immune‐escape mechanism; potential implications for checkpoint therapy though unproven<ref name=":0" />
	\|-		\|-
	\|'''STAT5B'''		\|'''STAT5B'''
Line 94:		Line 94:
	\|T / P		\|T / P
	\|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<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'''		\|'''STAT3'''
Line 103:		Line 103:
	\|T / P		\|T / P
	\|No		\|No
	\|Part of JAK/STAT alterations; less frequent than STAT5B in PCGDTCL		\|Part of JAK/STAT alterations; less frequent than STAT5B in PCGDTCL<ref name=":1" />
	\|-		\|-
	\|'''JAK3'''		\|'''JAK3'''
Line 112:		Line 112:
	\|T		\|T
	\|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<ref name=":0" />
	\|-		\|-
	\|'''KRAS'''		\|'''KRAS'''
Line 121:		Line 121:
	\|T / P		\|T / P
	\|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<ref name=":0" />
	\|-		\|-
	\|'''NRAS'''		\|'''NRAS'''
Line 130:		Line 130:
	\|T / P		\|T / P
	\|No		\|No
	\|Part of same pathway as KRAS though less common		\|Part of same pathway as KRAS though less common<ref name=":0" />
	\|-		\|-
	\|'''MYC'''		\|'''MYC'''
Line 139:		Line 139:
	\|P / T		\|P / T
	\|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<ref name=":0" />
	\|-		\|-
	\|'''MYCN'''		\|'''MYCN'''
Line 148:		Line 148:
	\|P / T		\|P / T
	\|No		\|No
	\|Highlights involvement of MYC family beyond MYC itself in PCGDTCL		\|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 157:
	\|D / P		\|D / P
	\|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<ref name=":0" />
	\|-		\|-
	\|'''Fusion: FYN :: (probable partner TRAF3IP2)'''		\|'''Fusion: FYN :: (probable partner TRAF3IP2)'''
Line 166:		Line 166:
	\|T		\|T
	\|No		\|No
	\|Very recently described; may represent novel driver/target; further cases needed		\|Very recently described; may represent novel driver/target; further cases needed<ref>{{Cite journal\|last=Azimpouran\|first=Mahzad\|last2=Bui\|first2=Chau M.\|last3=Balzer\|first3=Bonnie\|last4=Kitahara\|first4=Sumire\|date=2024-12-01\|title=Rapidly Progressive Primary Cutaneous Gamma Delta T-Cell Lymphoma With FYN Gene Alteration\|url=https://pubmed.ncbi.nlm.nih.gov/39412302\|journal=The American Journal of Dermatopathology\|volume=46\|issue=12\|pages=e120–e123\|doi=10.1097/DAD.0000000000002856\|issn=1533-0311\|pmid=39412302}}</ref>
	\|-		\|-
	\|'''Fusion: PCM1 :: JAK2'''		\|'''Fusion: PCM1 :: JAK2'''
Line 175:		Line 175:
	\|T		\|T
	\|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<ref name=":2">{{Cite journal\|last=Fadl\|first=Amr\|last2=Bennani\|first2=N. Nora\|last3=Comfere\|first3=Nneka\|last4=Durani\|first4=Urshila\|last5=Greipp\|first5=Patricia T.\|last6=Feldman\|first6=Andrew L.\|date=2023-09\|title=Primary cutaneous gamma/delta T-cell lymphoma with simultaneous JAK2 and TP63 rearrangements: a new double-hit?\|url=https://pubmed.ncbi.nlm.nih.gov/37308177\|journal=Histopathology\|volume=83\|issue=3\|pages=492–495\|doi=10.1111/his.14973\|issn=1365-2559\|pmc=10524708\|pmid=37308177}}</ref>
	\|-		\|-
	\|'''Fusion: TBL1XR1 :: TP63'''		\|'''Fusion: TBL1XR1 :: TP63'''
Line 184:		Line 184:
	\|P / T		\|P / T
	\|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<ref name=":2" />
	\|}		\|}
	==Individual Region Genomic Gain/Loss/LOH==		==Individual Region Genomic Gain/Loss/LOH==

← Older revision		Revision as of 15:51, 7 November 2025
Line 392:		Line 392:
	\|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'''
Line 400:		Line 400:
	\|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==
Line 411:		Line 411:
	\|-		\|-
	\|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
	\|}		\|}