期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-09644-6
关键词
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资金
- National Key Research and Development Program of China [2017YFC1308900]
- National Bio-Tech 863 Program [2012AA02A203]
- National Key R&D Program of China [2017YFC0908300, 2016YFC1303200]
- Beijing Nova Program [Z151100000315069]
- Beijing Talent Fund
- National Science Foundation of China [81772502]
- Beijing Municipal Commission of Health and Family Planning Project [PXM2018_026279_000005]
- Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201701]
- Guangzhou Health-Medical Collaborative Innovation Project [201508020247]
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.
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