Exome and genome sequencing of nasopharynx cancer identifies NF-?B pathway activating mutations.

ABSTRACT: Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-?B pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases. Functional analysis confirmed inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent membrane protein 1 (LMP1) functions to constitutively activate NF-?B signalling, and we observed mutual exclusivity among tumours with somatic NF-?B pathway aberrations and LMP1-overexpression, suggesting that NF-?B activation is selected for by both somatic and viral events during NPC pathogenesis.

SUBMITTER: Li YY 

PROVIDER: S-EPMC5253631 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature