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

Yvonne Y Li, Grace T. Y. Chung, Vivian W. Y. Lui, Ka-Fai To, Brigette B. Y. Ma, Chit Chow, S. Woo John K, 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. Verhoeft, Peony 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 () and Kwok-Wai Lo ()
Additional contact information
Yvonne Y Li: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, Cancer Program, Broad Institute of Harvard and MIT
Grace T. Y. Chung: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
Vivian W. Y. Lui: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong
Ka-Fai To: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
Brigette B. Y. Ma: State Key Laboratory of Oncology in South China, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong
Chit Chow: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
S. Woo John K: Head and Neck Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong
Kevin Y. Yip: The Chinese University of Hong Kong
Jeongsun Seo: Genomic Medicine Institute, Medical Research Center, Seoul National University
Edwin P. Hui: State Key Laboratory of Oncology in South China, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong
Michael K. F. Mak: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
Maria Rusan: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, Cancer Program, Broad Institute of Harvard and MIT
Nicole G. Chau: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, Cancer Program, Broad Institute of Harvard and MIT
Yvonne Y. Y. Or: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
Marcus H. N. Law: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
Peggy P. Y. Law: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
Zoey W. Y. Liu: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
Hoi-Lam Ngan: School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong
Pok-Man Hau: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
Krista R. Verhoeft: School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong
Peony H. Y. Poon: School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong
Seong-Keun Yoo: Genomic Medicine Institute, Medical Research Center, Seoul National University
Jong-Yeon Shin: Genomic Medicine Institute, Medical Research Center, Seoul National University
Sau-Dan Lee: The Chinese University of Hong Kong
Samantha W. M. Lun: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
Lin Jia: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Anthony W. H. Chan: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong
Jason Y. K. Chan: Head and Neck Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong
Paul B. S. Lai: Prince of Wales Hospital, The Chinese University of Hong Kong
Choi-Yi Fung: School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong
Suet-Ting Hung: School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong
Lin Wang: University of Pittsburgh Medical Center
Ann Margaret V. Chang: Institute of Pathology, St. Luke’s Medical Center
Simion I. Chiosea: University of Pittsburgh Medical Center
Matthew L. Hedberg: Medical Scientist Training Program, University of Pittsburgh–Carnegie Mellon University
Sai-Wah Tsao: School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Andrew C. van Hasselt: Head and Neck Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong
Anthony T. C. Chan: State Key Laboratory of Oncology in South China, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong
Jennifer R. Grandis: University of California San Francisco
Peter S. Hammerman: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, Cancer Program, Broad Institute of Harvard and MIT
Kwok-Wai Lo: State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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-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.

Date: 2017
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DOI: 10.1038/ncomms14121

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