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Exome and genome sequencing of nasopharynx cancer identifies NF-[kappa]B pathway activating mutations

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 wh...

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Bibliographic Details
Published in:Nature communications 2017-01, Vol.8, p.14121
Main Authors: 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
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Language:English
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Summary: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.
ISSN:2041-1723
DOI:10.1038/ncomms14121