51. Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma
- Author
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Victor Ho-Fun Lee, Ka-On Lam, Rebecca Kan, Maria Li Lung, Wai Tong Ng, Merrin Man Long Leong, Bonnie W.Y. Wong, Wing Sum Li, Roger Kai Cheong Ngan, Jimmy Yu-Wai Chan, Anne Wing-Mui Lee, Stewart Tung, Tommy Chin Tung Kwok, Josephine Mun Yee Ko, Wei Dai, Kwok Wah Chan, Hong Zheng, Mingdan Deng, Chun Chung Yau, Stephen S.-T. Yau, Dora L.W. Kwong, Chung Kong Kwan, and Arthur Kwok Leung Cheung
- Subjects
0301 basic medicine ,APOBEC ,Somatic cell ,APOBEC-mediated signature ,Biology ,medicine.disease_cause ,TNFAIP3 ,03 medical and health sciences ,0302 clinical medicine ,Mutation Rate ,NF-KappaB Inhibitor alpha ,Loss of Function Mutation ,Cell Line, Tumor ,Exome Sequencing ,medicine ,otorhinolaryngologic diseases ,Nasopharyngeal carcinoma ,Humans ,Loss function ,Exome sequencing ,Genetics ,Somatic mutation landscape ,Multidisciplinary ,Carcinoma ,NF-kappa B ,Nasopharyngeal Neoplasms ,Cytidine deaminase ,Biological Sciences ,medicine.disease ,stomatognathic diseases ,030104 developmental biology ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Whole-exome sequencing ,NF-κB signaling ,Carcinogenesis ,Signal Transduction - Abstract
Significance Host genetics, environmental factors, and EBV infection together contribute to nasopharyngeal carcinoma (NPC) development. A number of critical genetic and epigenetic events contributing to tumor development has been reported. However, the genomic alterations in NPC have not been completely deciphered. We used the whole-exome sequencing approach to study the somatic mutations in NPC, and an APOBEC-mediated mutagenesis signature was revealed. Importantly, multiple loss-of-function mutations in the NF-κB–negative regulators ( NFKBIA , CYLD , and TNFAIP3 ) were discovered in NPC tumors, and we functionally confirmed that the NFKBIA loss-of-function mutations induce damaging effects on the WT proteins. Detection of these mutations emphasizes the critical role of NF-κB signaling in NPC tumorigenesis and provides perspectives for targeting this pathway in NPC treatment.
- Published
- 2016