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Hodgkin lymphoma (HL) is characterized by a minority of B-cell-derived tumor cells, named Hodgkin Reed-Sternberg (HRS) cells in classical (c)HL and lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant (NLP) HL. HRS cells lack expression of the B-cell receptor in most cases and rely on activation of multiple pathways to escape from apoptosis in the germinal center (GC) reaction. Constitutive activation of the NF-κB pathway is achieved by activation of various signaling pathways, for example, CD30, CD40-CD40L and Epstein-Barr virus (EBV)-derived latent membrane protein 1 (LMP1). In addition, NF-κB activation is caused by diverse aberrations in multiple genes involved in the NF-κB pathway, such as amplifications of REL, gains of MAP3K14, mutations of TNFAIP3, NFKBIA and NFKBIE. A second pathway frequently altered in HRS cells is the JAK/STAT signaling pathway. Activation is caused by gains of JAK2 and inactivating mutations of SOCS1. In recent years, high-throughput sequencing technology has provided novel opportunities for the comprehensive identification of genetic aberrations involved in various types of cancer. To increase our understanding of the pathogenesis of HL, we performed whole-exome sequencing (WES) in seven cell lines to identify commonly mutated genes in HL.