Details

Autor(en) / Beteiligte

• Li, Yvonne Y
• Chung, Grace T Y
• Lui, Vivian W Y
• To, Ka-fai
• Ma, Brigette B Y
• Chow, Chit
• Woo, John K S
• Yip, Kevin Y
• Seo, Jeongsun
• Hui, Edwin P
• Mak, Michael K F
• Rusan, Maria
• Chau, Nicole G
• Or, Yvonne Y Y
• Law, Marcus H N
• Law, Peggy P Y
• Liu, Zoey W Y
• Ngan, Hoi-lam
• Hau, Pok-man
• Verhoeft, Krista R
• Poon, Peony H Y
• Yoo, Seong-keun
• Shin, Jong-yeon
• Lee, Sau-dan
• Lun, Samantha W M
• Jia, Lin
• Chan, Anthony W H
• Chan, Jason Y K
• Lai, Paul B S
• Fung, Choi-yi
• Hung, Suet-ting
• Wang, Lin
• Chang, Ann Margaret V
• Chiosea, Simion I
• Hedberg, Matthew L
• Tsao, Sai-wah
• Van Hasselt, Andrew C
• Chan, Anthony T C
• Grandis, Jennifer R
• Hammerman, Peter S
• Lo, Kwok-wai

Titel

Exome and genome sequencing of nasopharynx cancer identifies NF-[kappa]B pathway activating mutations

Ist Teil von

• Nature communications, 2017-01, Vol.8, p.14121

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.