HAEM5:Classic Hodgkin lymphoma: Difference between revisions

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 ==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==
@@ Line 341: / Line 341: @@
 !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==
-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==
-N/A
+Familial aggregation and monozygotic twin concordance suggest genetic predisposition (PMID: 26311361, 34208754)
 ==Additional Information==