Compendium of Cancer Genome Aberrations

HAEM5:Classic Hodgkin lymphoma: Difference between revisions

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{{DISPLAYTITLE:Classic Hodgkin lymphoma}}
{{DISPLAYTITLE:Classic Hodgkin lymphoma}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


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==Primary Author(s)*==
==Primary Author(s)*==


Patricia V. Hernandez, M.D., Washington University School of Medicine
Xiaolin Hu, Ph.D., GeneDx
==WHO Classification of Disease==
==WHO Classification of Disease==


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|}
|}


==WHO Essential and Desirable Genetic Diagnostic Criteria==
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
{| class="wikitable"
|+
|WHO Essential Criteria (Genetics)*
|
|-
|WHO Desirable Criteria (Genetics)*
|
|-
|Other Classification
|
|}
<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
==Related Terminology==
==Related Terminology==
<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
 
{| class="wikitable"
{| class="wikitable"
|+
|+
|Acceptable
|Acceptable
|
|N/A
|-
|-
|Not Recommended
|Not Recommended
|
|Hodgkin disease
|}
|}


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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''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>
|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)
|}
|}


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!Chromosomal Pattern
!Chromosomal Pattern
!Molecular Pathogenesis
!Molecular Pathogenesis
!'''Prevalence -'''
!Prevalence -  
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
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!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).
|}
|}


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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|TNFAIP3
|Inactivating mutation
|Tumor Suppressor Gene
|Recurrent (5-20%)
|P
|No
|Loss of function mutations disrupt NF-κB regulation (PMID: 19380639)
|-
|SOCS1
|Frameshift and nonsense mutations
|Tumor Suppressor Gene
|Recurrent (5-20%)
|P
|No
|SOCS1 mutations activate JAK/STAT signaling (PMID: 24531327)
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|STAT6
 
|Missense mutations
<br />
|Oncogene
|<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
|STAT6 mutations drive cytokine signaling alterations (PMID: 24531327, 29650799)
|<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
|B2M
<br />
|Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
|Tumor Suppressor Gene
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|Rare (<5%)
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
|P
|<span class="blue-text">EXAMPLE:</span> P
|No
|
|Loss of MHC class I expression aids immune evasion (PMID: 21368758)
|<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
|CIITA
|<span class="blue-text">EXAMPLE:</span> Activating mutations
|Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
|Tumor Suppressor Gene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|Rare (<5%)
|<span class="blue-text">EXAMPLE:</span> T
|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.


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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!Gene; Genetic Alteration!!Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)!!Prevalence (COSMIC /  TCGA / Other)!!Concomitant Mutations!!Mutually Exclusive Mutations
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
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==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==
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!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)
|-
|JAK2, STAT6, SOCS1
|JAK/STAT signaling
|Dysregulation leads to proliferation and survival of HRS cells (PMID: 24531327, 29650799)
|-
|-
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
|CD274 (PD-L1), PDCD1LG2 (PD-L2), B2M
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|Immune evasion
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|Upregulation of PD-L1/PD-L2 and loss of MHC I/II expression enables immune escape (PMID: 20628145, 21368758)
|-
|-
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
|EBV LMP1, LMP2A
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
|Viral oncogenesis
|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
|LMP1 mimics CD40 signaling, LMP2A mimics BCR signaling to promote HRS cell survival in EBV+ CHL (PMID: 9501091, 17682125)
|-
|-
|''REL'' (2p16), ''RELB'' (19q13), ''CD40'' (20q13) and ''MAP3K14'' (17q21)
|nuclear factor (NF)-κB signalling
|
|
|-
|
|''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)
*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).
*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==


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


==Additional Information==
==Additional Information==
Retrieved from "https://test.ccga.io/index.php/HAEM5:Classic_Hodgkin_lymphoma"