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, Australian Pancreatic Cancer Genome Initiative, Christian Pilarsky, Robert Grützmann, Michael J. Overman, Nigel B. Jamieson, George Van Buren, Jennifer Drummond, Kimberly Walker, Oliver A. HamptonLiu 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

Research output: Contribution to journalArticleResearchpeer-review

99 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)907-919
Number of pages13
JournalCell Reports
Issue number4
Publication statusPublished - 2 Feb 2016
Externally publishedYes

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