Compendium of Cancer Genome Aberrations

HAEM5:Classic Hodgkin lymphoma: Difference between revisions

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|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)
|}
|}


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


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!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).
|SOCS1
|Frameshift and nonsense mutations
|Tumor Suppressor Gene
|Recurrent (5-20%)
|P
|No
|SOCS1 mutations activate JAK/STAT signaling (PMID: 24531327)
|-
|STAT6
|Missense mutations
|Oncogene
|Recurrent (5-20%)
|P
|No
|STAT6 mutations drive cytokine signaling alterations (PMID: 24531327, 29650799)
|-
|-
|<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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==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)
|-
|-
|<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)
*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"