期刊
NATURE GENETICS
卷 46, 期 5, 页码 467-473出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2935
关键词
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资金
- National High-Tech R&D Program of China [2012AA02A503, 2012AA02A209]
- National Natural Science Foundation of China [81330052]
- US National Institutes of Health [R01CA026038-35]
- National Research Foundation Singapore
- Singapore Ministry of Education under Research Centers of Excellence
- Singapore Ministry of Health's National Medical Research Council under Singapore Translational Research (STaR) Investigator Award
Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized mutated genes such as FAT1, FAT2, ZNF750 and KMT2D, in addition to those already known (TP53, PIK3CA and NOTCH 1). Further SCNV evaluation, immunohistochemistry and biological analysis suggested their functional relevance in ESCC. Notably, RTK-MAPK-PI3K pathways, cell cycle and epigenetic regulation are frequently dysregulated by multiple molecular mechanisms in this cancer. Our approaches also uncovered many druggable candidates, and XPO1 was further explored as a therapeutic target because it showed both gene mutation and protein overexpression. Our integrated study unmasks a number of novel genetic lesions in ESCC and provides an important molecular foundation for understanding esophageal tumors and developing therapeutic targets.
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