期刊
CANCER CELL
卷 29, 期 2, 页码 229-240出版社
CELL PRESS
DOI: 10.1016/j.ccell.2015.12.012
关键词
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资金
- Ministry of Education, Culture, Science and Technology of Japan [25134719, 25134721, 25134720]
- Takeda Science Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Princess Takamatsu Cancer Research Fund
- National Cancer Center Research and Development Fund [25-A-3]
- Ministry of Health Labor and Welfare (Health and Labor Sciences Research Expenses for Commission and Applied Research for Innovative Treatment of Cancer)
- AIRC [12182]
- Italian Cancer Genome Project [FIRB RBAP10AHJB]
- US National Cancer Institutes SPORE grant [CA62924]
- Grants-in-Aid for Scientific Research [25860432] Funding Source: KAKEN
Ampullary carcinomas are highly malignant neoplasms that can have either intestinal or pancreatobiliary differentiation. To characterize somatic alterations in ampullary carcinomas, we performed whole-exome sequencing and DNA copy-number analysis on 60 ampullary carcinomas resected from clinically well-characterized Japanese and American patients. We next selected 92 genes and performed targeted sequencing to validate significantly mutated genes in an additional 112 cancers. The prevalence of driver gene mutations in carcinomas with the intestinal phenotype is different from those with the pancreatobiliary phenotype. We identified a characteristic significantly mutated driver gene (ELF3) as well as previously known driver genes (TP53, KRAS, APC, and others). Functional studies demonstrated that ELF3 silencing in normal human epithelial cells enhances their motility and invasion.
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