Compendium of Cancer Genome Aberrations

HAEM5:Classic Hodgkin lymphoma: Difference between revisions

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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==
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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|gain
|gain
|2p13
|2p13
|REL
|''REL''
|P
|P
|No
|No
|REL amplification promotes NF-κB signaling activation (PMID: 19380639)
|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 (PMID:20628145)
|Yes <ref name=":1" />
|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 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
|No
|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
|P
|No
|No
|MAP3K14 (NIK) gain activates alternative NF-κB signaling (PMID: 19380639)
|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 (PMID: 19380639)
|loss of tumor suppressors and contribute to HRS cell survival
|}
|}


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?


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!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?


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==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
N/A
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==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==
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