Author:
Zheng Hong,Dai Wei,Cheung Arthur Kwok Leung,Ko Josephine Mun Yee,Kan Rebecca,Wong Bonnie Wing Yan,Leong Merrin Man Long,Deng Mingdan,Kwok Tommy Chin Tung,Chan Jimmy Yu-Wai,Kwong Dora Lai-Wan,Lee Anne Wing-Mui,Ng Wai Tong,Ngan Roger Kai Cheong,Yau Chun Chung,Tung Stewart,Lee Victor Ho-fun,Lam Ka-On,Kwan Chung Kong,Li Wing Sum,Yau Stephen,Chan Kwok-Wah,Lung Maria Li
Abstract
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3. Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth. The identified loss-of-function mutations in NFKBIA leading to protein truncation contributed to the altered NF-κB activity, which is critical for NPC tumorigenesis. In addition, somatic mutations were found in several cancer-relevant pathways, including cell cycle-phase transition, cell death, EBV infection, and viral carcinogenesis. These data provide an enhanced road map for understanding the molecular basis underlying NPC.
Publisher
Proceedings of the National Academy of Sciences
Cited by
145 articles.
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