title: 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.
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan; Division of Cancer Genomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 1040045, Japan. Electronic address: syachida@ncc.go.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yachida
authors.affiliation: Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Takai
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Totoki
authors.affiliation: Department of Bioinformatics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchini
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Hama
authors.affiliation: Department of Bioinformatics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Asmaa
authors.initials: A
authors.lastname: Elzawahry
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Hosoda
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Shirota
authors.affiliation: Division of Medical Elemental Technology Development, Department of Advanced Analysis Technology, R&D Group, Olympus Corporation, Tokyo 1630914, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Morimoto
authors.affiliation: Division of Medical Elemental Technology Development, Department of Advanced Analysis Technology, R&D Group, Olympus Corporation, Tokyo 1630914, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Hori
authors.affiliation: Division of Medical Elemental Technology Development, Department of Advanced Analysis Technology, R&D Group, Olympus Corporation, Tokyo 1630914, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Funazaki
authors.affiliation: Division of Virology, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 1040045, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Morizane
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 1040045, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.affiliation: Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo 1040045, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nara
authors.affiliation: Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo 1040045, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 1040045, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.affiliation: Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 1040045, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo 1628666, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Higuchi
authors.affiliation: Department of Gastroenterological Surgery, Kagawa University, Kagawa 7610793, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Oshima
authors.affiliation: Department of Gastroenterological Surgery, Kagawa University, Kagawa 7610793, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Okano
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama 6418509, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Hirono
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai Miyagi 9808575, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Mizuma
authors.affiliation: Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima 7348551, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.affiliation: Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo 1628666, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai Miyagi 9808575, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama 6418509, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Weiss
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.affiliation: Institute for Integrated Medical Science, Tokyo Women's Medical University, Tokyo 1628666, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakagama
authors.affiliation: Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; The Ludwig Center and The Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.affiliation: Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo 1040045, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
authors.affiliation: Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan; Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors