| Autor: |
Hong Zheng, Wei Dai, Kwok Leung Cheung, Arthur, Mun Yee Ko, Josephine, Kan, Rebecca, Wing Yan Wong, Bonnie, Man Long Leong, Merrin, Mingdan Deng, Chin Tung Kwok, Tommy, Yu-Wai Chan, Jimmy, Lai-Wan Kwong, Dora, Wing-Mui Lee, Anne, Wai Tong Ng, Kai Cheong Ngan, Roger, Chun Chung Yau, Tung, Stewart, Ho-fun Lee, Victor, Ka-On Lam, Chung Kong Kwan, Wing Sum Li |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 10/4/2016, Vol. 113 Issue 40, p11283-11288, 6p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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