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Li, Yvonne Y; Chung, Grace T Y; Lui, Vivian W Y; To, Ka-Fai; Ma, Brigette B Y; Chow, Chit; Woo, John K S; Yip, Kevin Y; Seo, Jeongsun; Hui, Edwin P; Mak, Michael K F; Rusan, Maria; Chau, Nicole G; Or, Yvonne Y Y; Law, Marcus H N; Law, Peggy P Y; Liu, Zoey W Y; Ngan, Hoi-Lam; Hau, Pok-Man; Verhoeft, Krista R; Poon, Peony H Y; Yoo, Seong-Keun; Shin, Jong-Yeon; Lee, Sau-Dan; Lun, Samantha W M; Jia, Lin; Chan, Anthony W H; Chan, Jason Y K; Lai, Paul B S; Fung, Choi-Yi; Hung, Suet-Ting; Wang, Lin; Chang, Ann Margaret V; Chiosea, Simion I; Hedberg, Matthew L; Tsao, Sai-Wah; van Hasselt, Andrew C; Chan, Anthony T C; Grandis, Jennifer R; Hammerman, Peter S; Lo, Kwok-Wai
Nature communications, 01/2017, Letnik: 8, Številka: 1Journal Article
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-κB 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-κB signalling, and we observed mutual exclusivity among tumours with somatic NF-κB pathway aberrations and LMP1-overexpression, suggesting that NF-κB activation is selected for by both somatic and viral events during NPC pathogenesis.
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Vir: Osebne bibliografije
in: SICRIS
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