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Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma.


ABSTRACT: 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.

SUBMITTER: Yachida S 

PROVIDER: S-EPMC5503303 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma.

Yachida Shinichi S   Wood Laura D LD   Suzuki Masami M   Takai Erina E   Totoki Yasushi Y   Kato Mamoru M   Luchini Claudio C   Arai Yasuhito Y   Nakamura Hiromi H   Hama Natsuko N   Elzawahry Asmaa A   Hosoda Fumie F   Shirota Tomoki T   Morimoto Nobuhiko N   Hori Kunio K   Funazaki Jun J   Tanaka Hikaru H   Morizane Chigusa C   Okusaka Takuji T   Nara Satoshi S   Shimada Kazuaki K   Hiraoka Nobuyoshi N   Taniguchi Hirokazu H   Higuchi Ryota R   Oshima Minoru M   Okano Keiichi K   Hirono Seiko S   Mizuma Masamichi M   Arihiro Koji K   Yamamoto Masakazu M   Unno Michiaki M   Yamaue Hiroki H   Weiss Matthew J MJ   Wolfgang Christopher L CL   Furukawa Toru T   Nakagama Hitoshi H   Vogelstein Bert B   Kiyono Tohru T   Hruban Ralph H RH   Shibata Tatsuhiro T  

Cancer cell 20160121 2


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 dr  ...[more]

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