Cell Reports (Feb 2016)
Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation
- Marie-Claude Gingras,
- Kyle R. Covington,
- David K. Chang,
- Lawrence A. Donehower,
- Anthony J. Gill,
- Michael M. Ittmann,
- Chad J. Creighton,
- Amber L. Johns,
- Eve Shinbrot,
- Ninad Dewal,
- William E. Fisher,
- Christian Pilarsky,
- Robert Grützmann,
- Michael J. Overman,
- Nigel B. Jamieson,
- George Van Buren II,
- Jennifer Drummond,
- Kimberly Walker,
- Oliver A. Hampton,
- Liu Xi,
- Donna M. Muzny,
- Harsha Doddapaneni,
- Sandra L. Lee,
- Michelle Bellair,
- Jianhong Hu,
- Yi Han,
- Huyen H. Dinh,
- Mike Dahdouli,
- Jaswinder S. Samra,
- Peter Bailey,
- Nicola Waddell,
- John V. Pearson,
- Ivon Harliwong,
- Huamin Wang,
- Daniela Aust,
- Karin A. Oien,
- Ralph H. Hruban,
- Sally E. Hodges,
- Amy McElhany,
- Charupong Saengboonmee,
- Fraser R. Duthie,
- Sean M. Grimmond,
- Andrew V. Biankin,
- David A. Wheeler,
- Richard A. Gibbs
Affiliations
- Marie-Claude Gingras
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Kyle R. Covington
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- David K. Chang
- Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK
- Lawrence A. Donehower
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Anthony J. Gill
- The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia
- Michael M. Ittmann
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- Chad J. Creighton
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Amber L. Johns
- The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia
- Eve Shinbrot
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Ninad Dewal
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- William E. Fisher
- Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
- Christian Pilarsky
- Department of Surgery, TU Dresden, 01307 Dresden, Germany
- Robert Grützmann
- Department of Surgery, Universitätsklinikum Erlangen, 91054 Erlangen, Germany
- Michael J. Overman
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Nigel B. Jamieson
- Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK
- George Van Buren II
- Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
- Jennifer Drummond
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Kimberly Walker
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Oliver A. Hampton
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Liu Xi
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Donna M. Muzny
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Harsha Doddapaneni
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Sandra L. Lee
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Michelle Bellair
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Jianhong Hu
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Yi Han
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Huyen H. Dinh
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Mike Dahdouli
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Jaswinder S. Samra
- Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia
- Peter Bailey
- Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK
- Nicola Waddell
- Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia
- John V. Pearson
- Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia
- Ivon Harliwong
- Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia
- Huamin Wang
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Daniela Aust
- Department of Pathology, TU Dresden, 01307 Dresden, Germany
- Karin A. Oien
- Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK
- Ralph H. Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
- Sally E. Hodges
- Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
- Amy McElhany
- Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
- Charupong Saengboonmee
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Fraser R. Duthie
- Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK
- Sean M. Grimmond
- Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK
- Andrew V. Biankin
- Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK
- David A. Wheeler
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Richard A. Gibbs
- Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- DOI
- https://doi.org/10.1016/j.celrep.2015.12.005
- Journal volume & issue
-
Vol. 14,
no. 4
pp. 907 – 919
Abstract
The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis.
