1. Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation
- Author
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George Van Buren, Harsha Doddapaneni, David K. Chang, Ralph H. Hruban, Fraser Duthie, Charupong Saengboonmee, Michael J. Overman, Lawrence A. Donehower, Michelle Bellair, Jianhong Hu, Daniela Aust, Mike Dahdouli, Eve Shinbrot, Sean M. Grimmond, Kimberly Walker, Ninad Dewal, Amber L. Johns, David A. Wheeler, Sandra L. Lee, Liu Xi, Ivon Harliwong, Jennifer Drummond, Chad J. Creighton, John V. Pearson, Peter Bailey, Jaswinder S. Samra, Michael Ittmann, Amy L. McElhany, Yi Han, Robert Grützmann, Karin A. Oien, Christian Pilarsky, Huamin Wang, Marie-Claude Gingras, Richard A. Gibbs, Donna M. Muzny, William E. Fisher, Huyen Dinh, Sally E. Hodges, Andrew V. Biankin, Nigel B. Jamieson, Nicola Waddell, Kyle R. Covington, Anthony J. Gill, and Oliver A. Hampton
- Subjects
0301 basic medicine ,Genome instability ,Ampulla of Vater ,Tumor suppressor gene ,Molecular Sequence Data ,Biology ,Adenocarcinoma ,Bioinformatics ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Genomic Instability ,Article ,Base Sequence ,DNA-Binding Proteins ,Duodenal Neoplasms ,Humans ,Microsatellite Repeats ,Pancreatic Neoplasms ,Proto-Oncogene Proteins c-ets ,Transcription Factors ,Mutation ,Wnt Signaling Pathway ,03 medical and health sciences ,0302 clinical medicine ,medicine ,lcsh:QH301-705.5 ,Wnt signaling pathway ,Microsatellite instability ,Cancer ,medicine.disease ,digestive system diseases ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Cancer research - Abstract
SummaryThe 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.
- Published
- 2016