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- Title
Whole-genome sequencing reveals novel tandem-duplication hotspots and a prognostic mutational signature in gastric cancer.
- Authors
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
- Abstract
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. Structural variations in gastric cancer impact progression. Here, the authors perform whole-genome sequencing on 168 gastric cancer patients and identified tandem-duplications of super-enhancer ZFP36L2 in 10% of gastric cancer, and mutational signatures in tumors with cadherin 1 mutations that associated with poor prognoses.
- Publication
Nature Communications, 2019, Vol 10, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-09644-6