Details

Autor(en) / Beteiligte

• Xing, Rui
• Zhou, Yong
• Yu, Jun
• Yu, Yingyan
• Nie, Yongzhan
• Luo, Wen
• Yang, Chao
• Xiong, Teng
• Wu, William K K
• Li, Zhongwu
• Bing, Yang
• Lin, Shuye
• Zhang, Yaping
• Hu, Yingqi
• Li, Lin
• Han, Lijuan
• Yang, Chen
• Huang, Shaogang
• Huang, Suiping
• Zhou, Rui
• Li, Jing
• Wu, Kaichun
• Fan, Daiming
• Tang, Guangbo
• Dou, Jianhua
• Zhu, Zhenggang
• Ji, Jiafu
• Fang, Xiaodong
• Lu, Youyong

Titel

Whole-genome sequencing reveals novel tandem-duplication hotspots and a prognostic mutational signature in gastric cancer

Ist Teil von

• Nature communications, 2019-05, Vol.10 (1), p.2037-13, Article 2037

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2019

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Genome-wide analysis of genomic signatures might reveal novel mechanisms for gastric cancer (GC) tumorigenesis. Here, we analysis structural variations (SVs) and mutational signatures via whole-genome sequencing of 168 GCs. Our data demonstrates diverse models of complex SVs operative in GC, which lead to high-level amplification of oncogenes. We find varying proportion of tandem-duplications (TDs) among individuals and identify 24 TD hotspots involving well-established cancer genes such as CCND1, ERBB2 and MYC. Specifically, we nominate a novel hotspot involving the super-enhancer of ZFP36L2 presents in approximately 10% GCs from different cohorts, the oncogenic role of which is further confirmed by experimental data. In addition, our data reveal a mutational signature, specifically occurring in noncoding region, significantly enriched in tumors with cadherin 1 mutations, and associated with poor prognoses. Collectively, our data suggest that TDs might serve as an important mechanism for cancer gene activation and provide a novel signature for stratification.