HAEM5:Classic Hodgkin lymphoma - Revision history

Lynn.Hu: /* Individual Region Genomic Gain/Loss/LOH */

2026-01-11T21:47:56Z

Individual Region Genomic Gain/Loss/LOH

← Older revision		Revision as of 16:47, 11 January 2026
Line 83:		Line 83:
	\|gain		\|gain
	\|2p13		\|2p13
	\|REL		\|''REL''
	\|P		\|P
	\|No		\|No
	\|REL amplification promotes NF-κB signaling activation <ref>{{Cite journal\|last=Joos\|first=Stefan\|last2=Menz\|first2=Christiane K.\|last3=Wrobel\|first3=Gunnar\|last4=Siebert\|first4=Reiner\|last5=Gesk\|first5=Stefan\|last6=Ohl\|first6=Sibylle\|last7=Mechtersheimer\|first7=Gunhild\|last8=Trümper\|first8=Lorenz\|last9=Möller\|first9=Peter\|date=2002-02-15\|title=Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the short arm of chromosome 2\|url=https://pubmed.ncbi.nlm.nih.gov/11830490\|journal=Blood\|volume=99\|issue=4\|pages=1381–1387\|doi=10.1182/blood.v99.4.1381\|issn=0006-4971\|pmid=11830490}}</ref><ref>{{Cite journal\|last=Martín-Subero\|first=José I.\|last2=Gesk\|first2=Stefan\|last3=Harder\|first3=Lana\|last4=Sonoki\|first4=Takashi\|last5=Tucker\|first5=Philip W.\|last6=Schlegelberger\|first6=Brigitte\|last7=Grote\|first7=Werner\|last8=Novo\|first8=Francisco J.\|last9=Calasanz\|first9=María J.\|date=2002-02-15\|title=Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/11830502\|journal=Blood\|volume=99\|issue=4\|pages=1474–1477\|doi=10.1182/blood.v99.4.1474\|issn=0006-4971\|pmid=11830502}}</ref><ref name=":2">{{Cite journal\|last=Steidl\|first=Christian\|last2=Telenius\|first2=Adele\|last3=Shah\|first3=Sohrab P.\|last4=Farinha\|first4=Pedro\|last5=Barclay\|first5=Lorena\|last6=Boyle\|first6=Merrill\|last7=Connors\|first7=Joseph M.\|last8=Horsman\|first8=Douglas E.\|last9=Gascoyne\|first9=Randy D.\|date=2010-07-22\|title=Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome\|url=https://pubmed.ncbi.nlm.nih.gov/20339089\|journal=Blood\|volume=116\|issue=3\|pages=418–427\|doi=10.1182/blood-2009-12-257345\|issn=1528-0020\|pmid=20339089}}</ref>		\|REL amplification promotes NF-κB signaling activation that promotes HRS cell survival and proliferation.<ref>{{Cite journal\|last=Joos\|first=Stefan\|last2=Menz\|first2=Christiane K.\|last3=Wrobel\|first3=Gunnar\|last4=Siebert\|first4=Reiner\|last5=Gesk\|first5=Stefan\|last6=Ohl\|first6=Sibylle\|last7=Mechtersheimer\|first7=Gunhild\|last8=Trümper\|first8=Lorenz\|last9=Möller\|first9=Peter\|date=2002-02-15\|title=Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the short arm of chromosome 2\|url=https://pubmed.ncbi.nlm.nih.gov/11830490\|journal=Blood\|volume=99\|issue=4\|pages=1381–1387\|doi=10.1182/blood.v99.4.1381\|issn=0006-4971\|pmid=11830490}}</ref><ref>{{Cite journal\|last=Martín-Subero\|first=José I.\|last2=Gesk\|first2=Stefan\|last3=Harder\|first3=Lana\|last4=Sonoki\|first4=Takashi\|last5=Tucker\|first5=Philip W.\|last6=Schlegelberger\|first6=Brigitte\|last7=Grote\|first7=Werner\|last8=Novo\|first8=Francisco J.\|last9=Calasanz\|first9=María J.\|date=2002-02-15\|title=Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/11830502\|journal=Blood\|volume=99\|issue=4\|pages=1474–1477\|doi=10.1182/blood.v99.4.1474\|issn=0006-4971\|pmid=11830502}}</ref><ref name=":2">{{Cite journal\|last=Steidl\|first=Christian\|last2=Telenius\|first2=Adele\|last3=Shah\|first3=Sohrab P.\|last4=Farinha\|first4=Pedro\|last5=Barclay\|first5=Lorena\|last6=Boyle\|first6=Merrill\|last7=Connors\|first7=Joseph M.\|last8=Horsman\|first8=Douglas E.\|last9=Gascoyne\|first9=Randy D.\|date=2010-07-22\|title=Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome\|url=https://pubmed.ncbi.nlm.nih.gov/20339089\|journal=Blood\|volume=116\|issue=3\|pages=418–427\|doi=10.1182/blood-2009-12-257345\|issn=1528-0020\|pmid=20339089}}</ref>
	\|-		\|-
	\|9p		\|9p
	\|Gain		\|Gain
	\|9p24.1		\|9p24.1
	\|CD274 (PD-L1), PDCD1LG2 (PD-L2), JAK2		\|''CD274'' (PD-L1), ''PDCD1LG2'' (PD-L2), JAK2
	\|T, P		\|T, P
	\|Yes <ref name=":1" />		\|Yes <ref name=":1" />
	\|9p24.1 amplification drives PD-L1/PD-L2 overexpression~~, relevant~~ for immune checkpoint inhibitor therapy <ref name=":1">{{Cite journal\|last=Green\|first=Michael R.\|last2=Monti\|first2=Stefano\|last3=Rodig\|first3=Scott J.\|last4=Juszczynski\|first4=Przemyslaw\|last5=Currie\|first5=Treeve\|last6=O'Donnell\|first6=Evan\|last7=Chapuy\|first7=Bjoern\|last8=Takeyama\|first8=Kunihiko\|last9=Neuberg\|first9=Donna\|date=2010-10-28\|title=Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/20628145\|journal=Blood\|volume=116\|issue=17\|pages=3268–3277\|doi=10.1182/blood-2010-05-282780\|issn=1528-0020\|pmc=2995356\|pmid=20628145}}</ref><ref>{{Cite journal\|last=Roemer\|first=Margaretha G. M.\|last2=Advani\|first2=Ranjana H.\|last3=Ligon\|first3=Azra H.\|last4=Natkunam\|first4=Yasodha\|last5=Redd\|first5=Robert A.\|last6=Homer\|first6=Heather\|last7=Connelly\|first7=Courtney F.\|last8=Sun\|first8=Heather H.\|last9=Daadi\|first9=Sarah E.\|date=2016-08-10\|title=PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome\|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC5019753/\|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology\|volume=34\|issue=23\|pages=2690–2697\|doi=10.1200/JCO.2016.66.4482\|issn=1527-7755\|pmc=5019753\|pmid=27069084}}</ref>		\|9p24.1 amplification drives PD-L1/PD-L2 overexpression leading to immune suppression. Relevant for immune checkpoint inhibitor therapy <ref name=":1">{{Cite journal\|last=Green\|first=Michael R.\|last2=Monti\|first2=Stefano\|last3=Rodig\|first3=Scott J.\|last4=Juszczynski\|first4=Przemyslaw\|last5=Currie\|first5=Treeve\|last6=O'Donnell\|first6=Evan\|last7=Chapuy\|first7=Bjoern\|last8=Takeyama\|first8=Kunihiko\|last9=Neuberg\|first9=Donna\|date=2010-10-28\|title=Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/20628145\|journal=Blood\|volume=116\|issue=17\|pages=3268–3277\|doi=10.1182/blood-2010-05-282780\|issn=1528-0020\|pmc=2995356\|pmid=20628145}}</ref><ref>{{Cite journal\|last=Roemer\|first=Margaretha G. M.\|last2=Advani\|first2=Ranjana H.\|last3=Ligon\|first3=Azra H.\|last4=Natkunam\|first4=Yasodha\|last5=Redd\|first5=Robert A.\|last6=Homer\|first6=Heather\|last7=Connelly\|first7=Courtney F.\|last8=Sun\|first8=Heather H.\|last9=Daadi\|first9=Sarah E.\|date=2016-08-10\|title=PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome\|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC5019753/\|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology\|volume=34\|issue=23\|pages=2690–2697\|doi=10.1200/JCO.2016.66.4482\|issn=1527-7755\|pmc=5019753\|pmid=27069084}}</ref>
	\|-		\|-
	\|~~17p~~		\|17q
	\|Gain		\|Gain
	\|17q21		\|17q21
	\|MAP3K14		\|''MAP3K14''
	\|P		\|P
	\|No		\|No
	\|MAP3K14 (NIK) gain activates alternative NF-κB signaling <ref name=":2" />		\|MAP3K14 (NIK) gain activates alternative NF-κB signaling <ref name=":2" />
			\|-
			\|19q
			\|Gain
			\|19q13.3
			\|''RELB''
			\|P
			\|No
			\|Overexpression of RELB leads to enhanced NF-kB signaling and HRS cell survival. <ref>{{Cite journal\|last=Slovak\|first=Marilyn L.\|last2=Bedell\|first2=Victoria\|last3=Hsu\|first3=Ya-Hsuan\|last4=Estrine\|first4=Dolores B.\|last5=Nowak\|first5=Norma J.\|last6=Delioukina\|first6=Maria L.\|last7=Weiss\|first7=Lawrence M.\|last8=Smith\|first8=David D.\|last9=Forman\|first9=Stephen J.\|date=2011-05-15\|title=Molecular karyotypes of Hodgkin and Reed-Sternberg cells at disease onset reveal distinct copy number alterations in chemosensitive versus refractory Hodgkin lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/21385932\|journal=Clinical Cancer Research: An Official Journal of the American Association for Cancer Research\|volume=17\|issue=10\|pages=3443–3454\|doi=10.1158/1078-0432.CCR-10-1071\|issn=1557-3265\|pmc=3096736\|pmid=21385932}}</ref>
			\|-
			\|20q
			\|Gain
			\|20q13
			\|''CD40''
			\|P
			\|No
			\|Over expression of CD40 activates NF-kB signaling, promotes proliferation and immune evasion.<ref>{{Cite journal\|last=Alibrahim\|first=Mohamed N.\|last2=Gloghini\|first2=Annunziata\|last3=Carbone\|first3=Antonino\|date=2024-12-05\|title=Pathobiological Features and Therapeutic Opportunities Linked to TNF Family Member Expression in Classic Hodgkin Lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/39682256\|journal=Cancers\|volume=16\|issue=23\|pages=4070\|doi=10.3390/cancers16234070\|issn=2072-6694\|pmc=11640334\|pmid=39682256}}</ref><ref>{{Cite journal\|last=De Re\|first=Valli\|last2=Caggiari\|first2=Laura\|last3=Repetto\|first3=Ombretta\|last4=Mussolin\|first4=Lara\|last5=Mascarin\|first5=Maurizio\|date=2019-10-02\|title=Classical Hodgkin's Lymphoma in the Era of Immune Checkpoint Inhibition\|url=https://pubmed.ncbi.nlm.nih.gov/31581738\|journal=Journal of Clinical Medicine\|volume=8\|issue=10\|pages=1596\|doi=10.3390/jcm8101596\|issn=2077-0383\|pmc=6832444\|pmid=31581738}}</ref>
	\|-		\|-
	\|6q		\|6q
	\|Loss		\|Loss
	\|6q23-24		\|6q23-24
	\|TNFAIP3		\|''TNFAIP3''
			\|P
			\|No
			\|Loss of TNFAIP3 (A20), a negative regulator of NF‑κB, enhance NF-kB signling <ref name=":0">{{Cite journal\|last=Schmitz\|first=Roland\|last2=Hansmann\|first2=Martin-Leo\|last3=Bohle\|first3=Verena\|last4=Martin-Subero\|first4=Jose Ignacio\|last5=Hartmann\|first5=Sylvia\|last6=Mechtersheimer\|first6=Gunhild\|last7=Klapper\|first7=Wolfram\|last8=Vater\|first8=Inga\|last9=Giefing\|first9=Maciej\|date=2009-05-11\|title=TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/19380639\|journal=The Journal of Experimental Medicine\|volume=206\|issue=5\|pages=981–989\|doi=10.1084/jem.20090528\|issn=1540-9538\|pmc=2715030\|pmid=19380639}}</ref>
			\|-
			\|13q
			\|Loss
			\|13q14
			\|''RB1''
	\|P		\|P
	\|No		\|No
	\|~~Loss~~ of TNFAIP3 (A20) disrupts NF-κB regulation <ref name=":0">{{Cite journal\|last=Schmitz\|first=Roland\|last2=Hansmann\|first2=Martin-Leo\|last3=Bohle\|first3=Verena\|last4=Martin-Subero\|first4=Jose Ignacio\|last5=Hartmann\|first5=Sylvia\|last6=Mechtersheimer\|first6=Gunhild\|last7=Klapper\|first7=Wolfram\|last8=Vater\|first8=Inga\|last9=Giefing\|first9=Maciej\|date=2009-05-11\|title=TNFAIP3 (A20) is a tumor ~~suppressor gene in Hodgkin lymphoma~~ and ~~primary mediastinal B~~ cell lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/19380639\|journal=The Journal of Experimental Medicine\|volume=206\|issue=5\|pages=981–989\|doi=10.1084/jem.20090528\|issn=1540-9538\|pmc=2715030\|pmid=19380639}}</ref>		\|loss of tumor suppressors and contribute to HRS cell survival
	\|}		\|}

Lynn.Hu: /* Individual Region Genomic Gain/Loss/LOH */

2026-01-11T20:51:31Z

Individual Region Genomic Gain/Loss/LOH

← Older revision		Revision as of 15:51, 11 January 2026
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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>

			Recurrent chromosomal imbalances are characteristic of CHL and contribute to its pathogenesis. Frequent gains include 2p (''REL''), 9p24.1 (''JAK2'', ''CD274/PDL1'', ''PDCD1LG2/PDL2''), and 17q21 (''MAP3K14''), while recurrent losses include 6q23–q24 (''TNFAIP3''). These alterations support activation of NF-κB and JAK/STAT pathways, as well as immune evasion.
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
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	\|P		\|P
	\|No		\|No
	\|REL amplification promotes NF-κB signaling activation <ref ~~name~~=":0">{{Cite journal\|last=~~Schmitz~~\|first=~~Roland~~\|last2=~~Hansmann~~\|first2=~~Martin-Leo~~\|last3=~~Bohle~~\|first3=~~Verena~~\|last4=~~Martin-Subero~~\|first4=~~Jose Ignacio~~\|last5=~~Hartmann~~\|first5=~~Sylvia~~\|last6=~~Mechtersheimer~~\|first6=~~Gunhild~~\|last7=~~Klapper~~\|first7=~~Wolfram~~\|last8=~~Vater~~\|first8=~~Inga~~\|last9=~~Giefing~~\|first9=~~Maciej~~\|date=~~2009~~-05-11\|title=~~TNFAIP3 (A20) is a tumor suppressor gene~~ in Hodgkin ~~lymphoma and primary mediastinal B cell~~ lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/~~19380639~~\|journal=~~The Journal of Experimental Medicine~~\|volume=~~206~~\|issue=5\|pages=~~981–989~~\|doi=10.~~1084~~/~~jem~~.~~20090528~~\|issn=~~1540~~-~~9538~~\|~~pmc~~=~~2715030~~\|pmid=~~19380639~~}}</ref>		\|REL amplification promotes NF-κB signaling activation <ref>{{Cite journal\|last=Joos\|first=Stefan\|last2=Menz\|first2=Christiane K.\|last3=Wrobel\|first3=Gunnar\|last4=Siebert\|first4=Reiner\|last5=Gesk\|first5=Stefan\|last6=Ohl\|first6=Sibylle\|last7=Mechtersheimer\|first7=Gunhild\|last8=Trümper\|first8=Lorenz\|last9=Möller\|first9=Peter\|date=2002-02-15\|title=Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the short arm of chromosome 2\|url=https://pubmed.ncbi.nlm.nih.gov/11830490\|journal=Blood\|volume=99\|issue=4\|pages=1381–1387\|doi=10.1182/blood.v99.4.1381\|issn=0006-4971\|pmid=11830490}}</ref><ref>{{Cite journal\|last=Martín-Subero\|first=José I.\|last2=Gesk\|first2=Stefan\|last3=Harder\|first3=Lana\|last4=Sonoki\|first4=Takashi\|last5=Tucker\|first5=Philip W.\|last6=Schlegelberger\|first6=Brigitte\|last7=Grote\|first7=Werner\|last8=Novo\|first8=Francisco J.\|last9=Calasanz\|first9=María J.\|date=2002-02-15\|title=Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/11830502\|journal=Blood\|volume=99\|issue=4\|pages=1474–1477\|doi=10.1182/blood.v99.4.1474\|issn=0006-4971\|pmid=11830502}}</ref><ref name=":2">{{Cite journal\|last=Steidl\|first=Christian\|last2=Telenius\|first2=Adele\|last3=Shah\|first3=Sohrab P.\|last4=Farinha\|first4=Pedro\|last5=Barclay\|first5=Lorena\|last6=Boyle\|first6=Merrill\|last7=Connors\|first7=Joseph M.\|last8=Horsman\|first8=Douglas E.\|last9=Gascoyne\|first9=Randy D.\|date=2010-07-22\|title=Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome\|url=https://pubmed.ncbi.nlm.nih.gov/20339089\|journal=Blood\|volume=116\|issue=3\|pages=418–427\|doi=10.1182/blood-2009-12-257345\|issn=1528-0020\|pmid=20339089}}</ref>
	\|-		\|-
	\|9p		\|9p
Line 100:		Line 102:
	\|P		\|P
	\|No		\|No
	\|MAP3K14 (NIK) gain activates alternative NF-κB signaling <ref name=":0" />		\|MAP3K14 (NIK) gain activates alternative NF-κB signaling <ref name=":2" />
	\|-		\|-
	\|6q		\|6q
Line 108:		Line 110:
	\|P		\|P
	\|No		\|No
	\|Loss of TNFAIP3 (A20) disrupts NF-κB regulation <ref name=":0" />		\|Loss of TNFAIP3 (A20) disrupts NF-κB regulation <ref name=":0">{{Cite journal\|last=Schmitz\|first=Roland\|last2=Hansmann\|first2=Martin-Leo\|last3=Bohle\|first3=Verena\|last4=Martin-Subero\|first4=Jose Ignacio\|last5=Hartmann\|first5=Sylvia\|last6=Mechtersheimer\|first6=Gunhild\|last7=Klapper\|first7=Wolfram\|last8=Vater\|first8=Inga\|last9=Giefing\|first9=Maciej\|date=2009-05-11\|title=TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/19380639\|journal=The Journal of Experimental Medicine\|volume=206\|issue=5\|pages=981–989\|doi=10.1084/jem.20090528\|issn=1540-9538\|pmc=2715030\|pmid=19380639}}</ref>
	\|}		\|}

Lynn.Hu: /* Gene Rearrangements */

2025-11-21T04:27:34Z

Gene Rearrangements

← Older revision		Revision as of 23:27, 20 November 2025
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	\|CD274 (PD-L1), PDCD1LG2 (PD-L2), JAK2		\|CD274 (PD-L1), PDCD1LG2 (PD-L2), JAK2
	\|T, P		\|T, P
	\|Yes ~~(PMID~~:~~20628145)~~		\|Yes <ref name=":1" />
	\|9p24.1 amplification drives PD-L1/PD-L2 overexpression, relevant for immune checkpoint inhibitor therapy <ref>{{Cite journal\|last=Green\|first=Michael R.\|last2=Monti\|first2=Stefano\|last3=Rodig\|first3=Scott J.\|last4=Juszczynski\|first4=Przemyslaw\|last5=Currie\|first5=Treeve\|last6=O'Donnell\|first6=Evan\|last7=Chapuy\|first7=Bjoern\|last8=Takeyama\|first8=Kunihiko\|last9=Neuberg\|first9=Donna\|date=2010-10-28\|title=Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/20628145\|journal=Blood\|volume=116\|issue=17\|pages=3268–3277\|doi=10.1182/blood-2010-05-282780\|issn=1528-0020\|pmc=2995356\|pmid=20628145}}</ref><ref>{{Cite journal\|last=Roemer\|first=Margaretha G. M.\|last2=Advani\|first2=Ranjana H.\|last3=Ligon\|first3=Azra H.\|last4=Natkunam\|first4=Yasodha\|last5=Redd\|first5=Robert A.\|last6=Homer\|first6=Heather\|last7=Connelly\|first7=Courtney F.\|last8=Sun\|first8=Heather H.\|last9=Daadi\|first9=Sarah E.\|date=2016-08-10\|title=PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome\|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC5019753/\|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology\|volume=34\|issue=23\|pages=2690–2697\|doi=10.1200/JCO.2016.66.4482\|issn=1527-7755\|pmc=5019753\|pmid=27069084}}</ref>		\|9p24.1 amplification drives PD-L1/PD-L2 overexpression, relevant for immune checkpoint inhibitor therapy <ref name=":1">{{Cite journal\|last=Green\|first=Michael R.\|last2=Monti\|first2=Stefano\|last3=Rodig\|first3=Scott J.\|last4=Juszczynski\|first4=Przemyslaw\|last5=Currie\|first5=Treeve\|last6=O'Donnell\|first6=Evan\|last7=Chapuy\|first7=Bjoern\|last8=Takeyama\|first8=Kunihiko\|last9=Neuberg\|first9=Donna\|date=2010-10-28\|title=Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/20628145\|journal=Blood\|volume=116\|issue=17\|pages=3268–3277\|doi=10.1182/blood-2010-05-282780\|issn=1528-0020\|pmc=2995356\|pmid=20628145}}</ref><ref>{{Cite journal\|last=Roemer\|first=Margaretha G. M.\|last2=Advani\|first2=Ranjana H.\|last3=Ligon\|first3=Azra H.\|last4=Natkunam\|first4=Yasodha\|last5=Redd\|first5=Robert A.\|last6=Homer\|first6=Heather\|last7=Connelly\|first7=Courtney F.\|last8=Sun\|first8=Heather H.\|last9=Daadi\|first9=Sarah E.\|date=2016-08-10\|title=PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome\|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC5019753/\|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology\|volume=34\|issue=23\|pages=2690–2697\|doi=10.1200/JCO.2016.66.4482\|issn=1527-7755\|pmc=5019753\|pmid=27069084}}</ref>
	\|-		\|-
	\|17p		\|17p
Line 197:		Line 197:
	!Clinical Relevance Details/Other Notes		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|Aneuploidy
	~~Co-deletion of 1p and 18q~~		\|Chromosomal instability
	\|~~<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).~~		\|Common
	\|~~<span class="blue-text">EXAMPLE:</span>~~ Common ~~(Oligodendroglioma)~~		\|P
	\|~~<span class="blue-text">EXAMPLE:</span> D,~~ P		\|No
	\|		\|Common in HRS cells; associated with genomic instability and disease progression (PMID: 7632954)
	\|
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|Hypertetraploidy
	~~Microsatellite instability~~ - ~~hypermutated~~		\|Chromosomal duplication leading to genome-wide imbalance
	\|		\|Recurrent (5–20%)
	~~\|<span class="blue-text">EXAMPLE:</span> Common~~ (~~Endometrial carcinoma~~)		\|P
	\|~~<span class="blue-text">EXAMPLE:</span>~~ P~~, T~~		\|No
	\|		\|Frequently observed in CHL; reflects chromosomal instability (PMID: 7632954)
	\|
	\|-		\|-
	\|		\|Recurrent chromosomal imbalances (e.g., 2p, 9p, 17q gains; 6q loss)
	\|		\|Deregulated NF-κB and JAK/STAT signaling; immune evasion
	\|		\|Common (>20%)
	\|		\|P,T
	\|		\|Yes (PMID: 19380639, 20628145)
	\|		\|Involves REL, JAK2, PD-L1, PD-L2, TNFAIP3; contributes to pathogenesis and guides immunotherapy potential
	\|}		\|}

	~~No characteristic chromosomal patterns have been reported for lymphocyte-rich classical Hodgkin's lymphoma.~~		The below table can be deleted?

	{\| class="wikitable sortable"		{\| class="wikitable sortable"

Lynn.Hu: /* Primary Author(s)* */

2025-11-21T04:02:37Z

Primary Author(s)*

← Older revision		Revision as of 23:02, 20 November 2025
Line 68:		Line 68:
	\|		\|
	\|}		\|}

	~~No characteristic chromosomal rearrangements have been reported for lymphocyte-rich classical Hodgkin's lymphoma.~~

	==Individual Region Genomic Gain/Loss/LOH==		==Individual Region Genomic Gain/Loss/LOH==
Line 86:		Line 84:
	\|P		\|P
	\|No		\|No
	\|REL amplification promotes NF-κB signaling activation (~~PMID~~: 19380639)		\|REL amplification promotes NF-κB signaling activation <ref name=":0">{{Cite journal\|last=Schmitz\|first=Roland\|last2=Hansmann\|first2=Martin-Leo\|last3=Bohle\|first3=Verena\|last4=Martin-Subero\|first4=Jose Ignacio\|last5=Hartmann\|first5=Sylvia\|last6=Mechtersheimer\|first6=Gunhild\|last7=Klapper\|first7=Wolfram\|last8=Vater\|first8=Inga\|last9=Giefing\|first9=Maciej\|date=2009-05-11\|title=TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/19380639\|journal=The Journal of Experimental Medicine\|volume=206\|issue=5\|pages=981–989\|doi=10.1084/jem.20090528\|issn=1540-9538\|pmc=2715030\|pmid=19380639}}</ref>
	\|-		\|-
	\|9p		\|9p
Line 94:		Line 92:
	\|T, P		\|T, P
	\|Yes (PMID:20628145)		\|Yes (PMID:20628145)
	\|9p24.1 amplification drives PD-L1/PD-L2 overexpression, relevant for immune checkpoint inhibitor therapy ~~(PMID~~: 20628145, 27069084)		\|9p24.1 amplification drives PD-L1/PD-L2 overexpression, relevant for immune checkpoint inhibitor therapy <ref>{{Cite journal\|last=Green\|first=Michael R.\|last2=Monti\|first2=Stefano\|last3=Rodig\|first3=Scott J.\|last4=Juszczynski\|first4=Przemyslaw\|last5=Currie\|first5=Treeve\|last6=O'Donnell\|first6=Evan\|last7=Chapuy\|first7=Bjoern\|last8=Takeyama\|first8=Kunihiko\|last9=Neuberg\|first9=Donna\|date=2010-10-28\|title=Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma\|url=https://pubmed.ncbi.nlm.nih.gov/20628145\|journal=Blood\|volume=116\|issue=17\|pages=3268–3277\|doi=10.1182/blood-2010-05-282780\|issn=1528-0020\|pmc=2995356\|pmid=20628145}}</ref><ref>{{Cite journal\|last=Roemer\|first=Margaretha G. M.\|last2=Advani\|first2=Ranjana H.\|last3=Ligon\|first3=Azra H.\|last4=Natkunam\|first4=Yasodha\|last5=Redd\|first5=Robert A.\|last6=Homer\|first6=Heather\|last7=Connelly\|first7=Courtney F.\|last8=Sun\|first8=Heather H.\|last9=Daadi\|first9=Sarah E.\|date=2016-08-10\|title=PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome\|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC5019753/\|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology\|volume=34\|issue=23\|pages=2690–2697\|doi=10.1200/JCO.2016.66.4482\|issn=1527-7755\|pmc=5019753\|pmid=27069084}}</ref>
	\|-		\|-
	\|17p		\|17p
Line 102:		Line 100:
	\|P		\|P
	\|No		\|No
	\|MAP3K14 (NIK) gain activates alternative NF-κB signaling ~~(PMID~~: ~~19380639)~~		\|MAP3K14 (NIK) gain activates alternative NF-κB signaling <ref name=":0" />
	\|-		\|-
	\|6q		\|6q
Line 110:		Line 108:
	\|P		\|P
	\|No		\|No
	\|Loss of TNFAIP3 (A20) disrupts NF-κB regulation ~~(PMID~~: ~~19380639)~~		\|Loss of TNFAIP3 (A20) disrupts NF-κB regulation <ref name=":0" />
	\|}		\|}

	~~There is no typical findings for lymphocyte-rich classical Hodgkin's lymphoma~~, ~~the main features are also seen in other classical Hodgkin's lymphoma subtypes.~~		The table below seems duplicated, can be deleted?

	{\| class="wikitable sortable"		{\| class="wikitable sortable"
Line 335:		Line 333:

	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==

	~~N/A~~
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-

Lynn.Hu: /* Genetic Diagnostic Testing Methods */

2025-07-12T13:19:15Z

Genetic Diagnostic Testing Methods

← Older revision		Revision as of 08:19, 12 July 2025
Line 363:		Line 363:
	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

	* Immunohistochemistry for CD30, CD15, PAX5, and EBV (EBER in situ hybridization) (PMID: 2477085, 6946981)		*Immunohistochemistry for CD30, CD15, PAX5, and EBV (EBER in situ hybridization) (PMID: 2477085, 6946981)
	* Targeted NGS panels for NF-κB and JAK/STAT pathway mutations (PMID: 33686198)		*9p24.1 copy number assessment (FISH or NGS) may be used in refractory/relapsed cases to evaluate PD-L1/PD-L2 amplification for potential immunotherapy (PMID: 29394125).
	* 9p24.1 copy number assessment ~~for~~ PD-L1/PD-L2 amplification in ~~refractory disease~~ (PMID: ~~29394125~~)		*TR clonality assays can help exclude T-cell lymphomas in challenging differential diagnoses (PMID: 24128129).
			*Targeted NGS panels for NF-κB and JAK/STAT pathway mutations (PMID: 33686198)

	==Familial Forms==		==Familial Forms==

Lynn.Hu: /* Epigenomic Alterations */

2025-07-11T19:06:03Z

Epigenomic Alterations

← Older revision		Revision as of 14:06, 11 July 2025
Line 332:		Line 332:
	==Epigenomic Alterations==		==Epigenomic Alterations==

	~~N/A~~		Global downregulation of B-cell transcription factors (OCT2, BOB1, PU.1) and epigenetic silencing of B-cell program genes (PMID: 19465900, 14694522)

	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==
Line 341:		Line 341:
	!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome		!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations~~		\|REL, TNFAIP3, NFKBIA, MAP3K14
	\|~~<span class="blue~~-~~text">EXAMPLE:</span> MAPK~~ signaling		\|NF-κB signaling
	\|~~<span class="blue~~-~~text">EXAMPLE~~:~~</span> Increased cell growth and proliferation~~		\|Constitutive activation of classical and alternative NF-κB pathways promotes HRS cell survival (PMID: 19380639, 33686198)
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations~~		\|JAK2, STAT6, SOCS1
	\|~~<span class="blue-text">EXAMPLE:<~~/~~span> Cell cycle regulation~~		\|JAK/STAT signaling
	\|~~<span class="blue-text">EXAMPLE~~:~~</span> Unregulated cell division~~		\|Dysregulation leads to proliferation and survival of HRS cells (PMID: 24531327, 29650799)
	\|-		\|-
	\|~~<span class="blue~~-~~text">EXAMPLE:</span> KMT2C and ARID1A; Inactivating mutations~~		\|CD274 (PD-L1), PDCD1LG2 (PD-L2), B2M
	\|~~<span class="blue~~-~~text">EXAMPLE:<~~/~~span> Histone modification, chromatin remodeling~~		\|Immune evasion
	~~\|<span class="blue~~-~~text">EXAMPLE:<~~/~~span> Abnormal gene~~ expression ~~program~~		\|Upregulation of PD-L1/PD-L2 and loss of MHC I/II expression enables immune escape (PMID: 20628145, 21368758)
	\|-		\|-
	\|~~''REL'' (2p16)~~, ~~''RELB''~~ (~~19q13)~~, ~~''CD40'' (20q13) and ''MAP3K14'' (17q21~~)		\|EBV LMP1, LMP2A
	\|~~nuclear factor (NF)~~-~~κB signalling~~		\|Viral oncogenesis
			\|LMP1 mimics CD40 signaling, LMP2A mimics BCR signaling to promote HRS cell survival in EBV+ CHL (PMID: 9501091, 17682125)
			\|-
			\|
	\|		\|
	\|-
	~~\|''JAK2'' amplification~~
	~~\|PD-L1 protein expression/ JAK/STAT pathway~~
	\|		\|
	\|}		\|}
	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

	N/A		* Immunohistochemistry for CD30, CD15, PAX5, and EBV (EBER in situ hybridization) (PMID: 2477085, 6946981)
			* Targeted NGS panels for NF-κB and JAK/STAT pathway mutations (PMID: 33686198)
			* 9p24.1 copy number assessment for PD-L1/PD-L2 amplification in refractory disease (PMID: 29394125)

	==Familial Forms==		==Familial Forms==

	~~N/A~~		Familial aggregation and monozygotic twin concordance suggest genetic predisposition (PMID: 26311361, 34208754)

	==Additional Information==		==Additional Information==

Lynn.Hu: /* Gene Mutations (SNV/INDEL) */

2025-07-11T19:02:20Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 14:02, 11 July 2025
Line 250:		Line 250:
	!Clinical Relevance Details/Other Notes		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span>''EGFR''~~		\|TNFAIP3
			\|Inactivating mutation
	~~<br />~~		\|Tumor Suppressor Gene
	\|~~<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations~~		\|Recurrent (5-20%)
	\|~~<span class="blue-text">EXAMPLE:</span> Oncogene~~		\|P
	\|~~<span class="blue~~-~~text">EXAMPLE:</span> Common (lung cancer~~)		\|No
	\|~~<span class="blue-text">EXAMPLE:</span> T~~		\|Loss of function mutations disrupt NF-κB regulation (PMID: 19380639)
	\|~~<span class="blue-text">EXAMPLE:</span> Yes (NCCN)~~
	\|~~<span class="blue~~-~~text">EXAMPLE~~:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations~~		\|SOCS1
	~~<br />~~		\|Frameshift and nonsense mutations
	\|~~<span class="blue-text">EXAMPLE:</span> Variable LOF~~ mutations		\|Tumor Suppressor Gene
	\|~~<span class="blue-text">EXAMPLE:</span>~~ Tumor ~~Supressor~~ Gene		\|Recurrent (5-20%)
	\|~~<span class="blue~~-~~text">EXAMPLE:</span> Common (breast cancer~~)		\|P
	\|~~<span class="blue-text">EXAMPLE:</span>~~ P		\|No
	\|		\|SOCS1 mutations activate JAK/STAT signaling (PMID: 24531327)
	\|~~<span class="blue-text">EXAMPLE:<~~/~~span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome~~ (~~add reference~~)~~. Denotes a poor prognosis in breast cancer.~~
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations~~		\|STAT6
	\|~~<span class="blue-text">EXAMPLE:</span> Activating~~ mutations		\|Missense mutations
	\|~~<span class="blue-text">EXAMPLE:</span>~~ Oncogene		\|Oncogene
	\|~~<span class="blue~~-~~text">EXAMPLE:</span> Common (melanoma~~)		\|Recurrent (5-20%)
	\|~~<span class="blue-text">EXAMPLE:</span> T~~		\|P
	\|		\|No
	\|		\|STAT6 mutations drive cytokine signaling alterations (PMID: 24531327, 29650799)
	\|-		\|-
	\|		\|B2M
	\|		\|Inactivating mutations
	\|		\|Tumor Suppressor Gene
	\|		\|Rare (<5%)
	\|		\|P
	\|		\|No
	\|		\|Loss of MHC class I expression aids immune evasion (PMID: 21368758)
			\|-
			\|CIITA
			\|Inactivating mutations
			\|Tumor Suppressor Gene
			\|Rare (<5%)
			\|P
			\|No
			\|Loss of MHC class II expression aids immune evasion (PMID: 21368758)
			\|-
			\|XPO1
			\|Missense mutations
			\|Oncogene
			\|Rare (<5%)
			\|Unknown
			\|No
			\|Emerging evidence of role in CHL pathogenesis (PMID: 33686198)
	\|}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.

Lynn.Hu: /* Characteristic Chromosomal or Other Global Mutational Patterns */

2025-07-11T18:59:39Z

Characteristic Chromosomal or Other Global Mutational Patterns

← Older revision		Revision as of 13:59, 11 July 2025
Line 233:		Line 233:
	!Notes		!Notes
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|Aneuploidy, hypertetraploidy

	~~Co-deletion of 1p and 18q~~
	~~\|Yes~~
	\|No		\|No
	\|No		\|unkonwn
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|unknown
			\|Common in HRS cells; contributes to genomic instability (PMID: 7632954)
	~~See chromosomal rearrangements table as this pattern is due~~ to ~~an unbalanced derivative translocation associated with oligodendroglioma~~ (~~add reference~~).
	\|}		\|}

Lynn.Hu: /* Individual Region Genomic Gain/Loss/LOH */

2025-07-11T18:53:26Z

Individual Region Genomic Gain/Loss/LOH

← Older revision		Revision as of 13:53, 11 July 2025
Line 96:		Line 96:
	\|9p24.1 amplification drives PD-L1/PD-L2 overexpression, relevant for immune checkpoint inhibitor therapy (PMID: 20628145, 27069084)		\|9p24.1 amplification drives PD-L1/PD-L2 overexpression, relevant for immune checkpoint inhibitor therapy (PMID: 20628145, 27069084)
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|17p
	17		\|Gain
	\|~~<span class="blue-text">EXAMPLE:</span> Amp~~		\|17q21
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|MAP3K14
	~~17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]~~		\|P
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|No
	~~''ERBB2''~~		\|MAP3K14 (NIK) gain activates alternative NF-κB signaling (PMID: 19380639)
	\|~~<span class="blue-text">EXAMPLE:</span> D,~~ P~~, T~~
	\|
	\|~~<span class="blue~~-~~text">EXAMPLE~~:~~</span>~~
	~~Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references~~)~~. Add criteria for how amplification is defined.~~
	\|-		\|-
	\|		\|6q
	\|		\|Loss
	\|		\|6q23-24
	\|		\|TNFAIP3
	\|		\|P
	\|		\|No
	\|		\|Loss of TNFAIP3 (A20) disrupts NF-κB regulation (PMID: 19380639)
	\|}		\|}

Lynn.Hu: /* Individual Region Genomic Gain/Loss/LOH */

2025-07-11T18:01:05Z

Individual Region Genomic Gain/Loss/LOH

← Older revision		Revision as of 13:01, 11 July 2025
Line 80:		Line 80:
	!Clinical Relevance Details/Other Notes		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|2p
	7		\|gain
	\|~~<span class="blue-text">EXAMPLE:</span> Loss~~		\|2p13
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|REL
	~~chr7~~		\|P
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|No
	~~Unknown~~		\|REL amplification promotes NF-κB signaling activation (PMID: 19380639)
	\|~~<span class="blue-text">EXAMPLE:</span> D,~~ P
	\|~~<span class="blue-text">EXAMPLE:</span>~~ No
	\|~~<span class="blue~~-~~text">EXAMPLE~~:~~</span>~~
	Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
	\|-		\|-
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|9p
	8		\|Gain
	\|~~<span class="blue-text">EXAMPLE:</span>~~ Gain		\|9p24.1
	\|~~<span class="blue-text">EXAMPLE:</span>~~		\|CD274 (PD-L1), PDCD1LG2 (PD-L2), JAK2
	~~chr8~~		\|T, P
	\|~~<span class="blue~~-~~text">EXAMPLE:</span>~~		\|Yes (PMID:20628145)
	~~Unknown~~		\|9p24.1 amplification drives PD-L1/PD-L2 overexpression, relevant for immune checkpoint inhibitor therapy (PMID: 20628145, 27069084)
	\|~~<span class="blue-text">EXAMPLE:</span> D~~, P
	\|
	\|~~<span class="blue~~-~~text">EXAMPLE:<~~/~~span>~~
	~~Common recurrent secondary finding~~ for t(~~8;21) (add references~~).
	\|-		\|-
	\|<span class="blue-text">EXAMPLE:</span>		\|<span class="blue-text">EXAMPLE:</span>