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

Yvonne Y. Li, Grace T.Y. Chung, Vivian W.Y. Lui, Ka Fai To, Brigette B.Y. Ma, Chit Chow, John K.S. Woo, Kevin Y. Yip, Jeongsun Seo, Edwin P. Hui, Michael K.F. Mak, Maria Rusan, Nicole G. Chau, Yvonne Y.Y. Or, Marcus H.N. Law, Peggy P.Y. Law, Zoey W.Y. Liu, Hoi Lam Ngan, Pok Man Hau, Krista R. VerhoeftPeony H.Y. Poon, Seong Keun Yoo, Jong Yeon Shin, Sau Dan Lee, Samantha W.M. Lun, Lin Jia, Anthony W.H. Chan, Jason Y.K. Chan, Paul B.S. Lai, Choi Yi Fung, Suet Ting Hung, Lin Wang, Ann Margaret V. Chang, Simion I. Chiosea, Matthew L. Hedberg, Sai Wah Tsao, Andrew C. Van Hasselt, Anthony T.C. Chan, Jennifer R. Grandis, Peter S. Hammerman, Kwok Wai Lo

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

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.

Original languageEnglish (US)
Article number14121
JournalNature communications
Volume8
DOIs
StatePublished - Jan 18 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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