Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations
| Autor: | Jason Y. K. Chan, Suet-Ting Hung, Lin Jia, Michael K. F. Mak, Maria Rusan, Jeong-Sun Seo, Brigette B.Y. Ma, Pok Man Hau, Zoey Wing Yee Liu, Ka Fai To, Anthony W.H. Chan, Matthew L. Hedberg, Jong-Yeon Shin, Hoi-Lam Ngan, Peter S. Hammerman, Kevin Y. Yip, Paul B.S. Lai, Samantha Wei-Man Lun, Anthony T.C. Chan, Andrew van Hasselt, Choi-Yi Fung, Yvonne Y. Li, Sau Dan Lee, Ann Margaret V. Chang, Edwin P. Hui, Krista Roberta Verhoeft, Seong Keun Yoo, Simion I. Chiosea, Sai Wah Tsao, Woo, John K, S., Peggy P.Y. Law, Peony Hiu Yan Poon, Yvonne Y. Y. Or, Vivian Wai Yan Lui, Lin Wang, Chit Chow, Kwok Wai Lo, Jennifer R. Grandis, Marcus H. N. Law, Grace Tin-Yun Chung, Nicole G. Chau |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Epstein-Barr Virus Infections Herpesvirus 4 Human Somatic cell General Physics and Astronomy medicine.disease_cause Genome NF-KappaB Inhibitor alpha Exome Cancer Genetics Mutation Multidisciplinary Nasopharyngeal Carcinoma NF-kappa B 3. Good health Deubiquitinating Enzyme CYLD HIV/AIDS Human Biotechnology Signal Transduction Science Biology General Biochemistry Genetics and Molecular Biology DNA sequencing Article Viral Matrix Proteins 03 medical and health sciences Rare Diseases Clinical Research medicine otorhinolaryngologic diseases Humans Dental/Oral and Craniofacial Disease Cell Proliferation Whole genome sequencing TNF Receptor-Associated Factor 3 Whole Genome Sequencing Genome Human Human Genome Carcinoma Herpesvirus 4 Nasopharyngeal Neoplasms General Chemistry medicine.disease stomatognathic diseases 030104 developmental biology Nasopharyngeal carcinoma Cancer research |
| Zdroj: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-10 (2017) Nature communications, vol 8, iss 1 |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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