Yvonne Y Li 1 , Grace T. Y. Chung 2 , Vivian W. Y. Lui 3 , 4 , Ka-Fai To 2 , Brigette B. Y. Ma 5 , Chit Chow 2 , John K, S. Woo 6 , Kevin Y. Yip 7 , Jeongsun Seo 8 , Edwin P. Hui 5 , Michael K. F. Mak 2 , Maria Rusan 1 , Nicole G. Chau 1 , Yvonne Y. Y. Or 2 , Marcus H. N. Law 2 , Peggy P. Y. Law 2 , Zoey W. Y. Liu 2 , Hoi-Lam Ngan 4 , Pok-Man Hau 2 , Krista R. Verhoeft 4 , Peony H. Y. Poon 4 , Seong-Keun Yoo 8 , Jong-Yeon Shin 8 , Sau-Dan Lee 7 , Samantha W. M. Lun 2 , Lin Jia 9 , Anthony W. H. Chan 2 , Jason Y. K. Chan 6 , Paul B. S. Lai 10 , Choi-Yi Fung 4 , Suet-Ting Hung 4 , Lin Wang 11 , Ann Margaret V. Chang 12 , Simion I. Chiosea 11 , Matthew L. Hedberg 13 , Sai-Wah Tsao 9 , Andrew C. van Hasselt 6 , Anthony T. C. Chan 5 , Jennifer R. Grandis 14 , Peter S. Hammerman a , 1 , Kwok-Wai Lo b , 2
18 January 2017
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.
Nasopharyngeal cancer is frequently characterized by Epstein-Barr virus infection. Here, using genomic analyses, the authors find that the tumours harbour mutations in genes involved in the NF-κB signalling pathway or overexpress a viral oncoprotein, latent membrane protein 1.