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      Genomic sequencing identifies ELF3 as a driver of ampullary carcinoma

      research-article
      1 , 20 , 2 , 1 , 1 , 1 , 3 , 2 , 1 , 1 , 1 , 3 , 1 , 1 , 4 , 4 , 4 , 5 , 6 , 6 , 7 , 7 , 8 , 8 , 9 , 10 , 10 , 11 , 12 , 13 , 9 , 12 , 11 , 14 , 14 , 15 , 16 , 2 , 17 , 16 , 2 , 18 , 1 , 19
      Cancer cell

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          SUMMARY

          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 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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          Author and article information

          Journal
          101130617
          29778
          Cancer Cell
          Cancer Cell
          Cancer cell
          1535-6108
          1878-3686
          29 April 2017
          21 January 2016
          08 February 2016
          10 July 2017
          : 29
          : 2
          : 229-240
          Affiliations
          [1 ]Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 1040045, Japan
          [2 ]Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
          [3 ]Department of Bioinformatics, National Cancer Center Research Institute, Tokyo 1040045, Japan
          [4 ]Division of Medical Elemental Technology Development, Department of Advanced Analysis Technology, R&D Group, Olympus Corporation, Tokyo 1630914, Japan
          [5 ]Division of Virology, National Cancer Center Research Institute, Tokyo 1040045, Japan
          [6 ]Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 1040045, Japan
          [7 ]Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo 1040045, Japan
          [8 ]Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 1040045, Japan
          [9 ]Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo 1628666, Japan
          [10 ]Department of Gastroenterological Surgery, Kagawa University, Kagawa 7610793, Japan
          [11 ]Second Department of Surgery, Wakayama Medical University, Wakayama 6418509, Japan
          [12 ]Department of Surgery, Tohoku University Graduate School of Medicine, Sendai Miyagi 9808575, Japan
          [13 ]Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima 7348551, Japan
          [14 ]Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
          [15 ]Institute for Integrated Medical Science, Tokyo Women’s Medical University, Tokyo 1628666, Japan
          [16 ]Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo 1040045, Japan
          [17 ]The Ludwig Center and The Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA
          [18 ]Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
          [19 ]Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan
          [20 ]Division of Cancer Genomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 1040045, Japan
          Author notes
          [* ]Address Correspondence to: Shinichi Yachida, MD, PhD, Laboratory Head, Division of Cancer Genomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 1040045, Japan, syachida@ 123456ncc.go.jp , Fax: +81(3)3545-3567, Tel: +81(3)3542-2511
          Article
          PMC5503303 PMC5503303 5503303 nihpa868704
          10.1016/j.ccell.2015.12.012
          5503303
          26806338
          bdeb7541-b2c7-464a-9e1f-0e4afa4e7688
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