Exome and Genome Sequencing of Nasopharynx Cancer Identifies NF-kB Pathway Activating Mutations
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AbstractNasopharyngeal 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-kappa 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-kappa B signalling, and we observed mutual exclusivity among tumours with somatic NF-kappa B pathway aberrations and LMP1-overexpression, suggesting that NF-kB activation is selected for by both somatic and viral events during NPC pathogenesis.
All Author(s) ListYvonne Y Li, Grace Tin-Yun Chung, Vivian W.Y. Lui, Ka-Fai To, Brigette Buig-Yue Ma, Chit Chow, John Kong-Sang Woo, Kevin Y. Yip, Jeongsun Seo, Edwin Pun Hui, Michael Ko-Fung Mak, Maria Rusan, Nicole G. Chau, Yvonne Yan-Yan Or, Marcus Hung-Nam Law, Peggy Pui-Ying Law, Zoey Wing-Yee Liu, Hoi Lam Ngan, Krista R. Verhoeft, Peony H.Y. Poon, Seong-Keun Yoo, Jong-Yeon Shin, Sau-Dan Lee, Samantha Wei-Man Lun, Anthony Wing-Hung Chan, Jason Ying-Kuen Chan, Paul Bo-San Lai, Choi-Yi Fung, Suet-Ting Hung, Lin Wang Lin, Ann Margaret V. Chang, Simion I. Chiosea, Matthew Louis Hedberg, Sai-Wah Tsao, Charles Andrew van Hasselt, Anthony Tak-Cheung Chan, Jennifer R. Grandis, Peter S. Hammerman, Kwok-Wai Lo
Journal nameNature Communications
Volume Number8
LanguagesEnglish-United States

Last updated on 2022-14-01 at 01:10