Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation

Gingras MC, Covington KR, Chang DK, Donehower LA, Gill AJ, Ittmann MM, Creighton CJ, Johns AL, Shinbrot E, Dewal N, Fisher WE, Pilarsky C, Grützmann R, Overman MJ, Jamieson NB, Van Buren G, Drummond J, Walker K, Hampton OA, Xi L, Muzny DM, Doddapaneni H, Lee SL, Bellair M, Hu J, Han Y, Dinh HH, Dahdouli M, Samra JS, Bailey P, Waddell N, Pearson JV, Harliwong I, Wang H, Aust D, Oien KA, Hruban RH, Hodges SE, Mcelhany A, Saengboonmee C, Duthie FR, Grimmond SM, Biankin AV, Wheeler DA, Gibbs RA, Pilarsky C (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 14

Pages Range: 907-19

Journal Issue: 4

DOI: 10.1016/j.celrep.2015.12.005

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 ?-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis.

Authors with CRIS profile

Robert Grützmann Department of Surgery Christian Pilarsky Professur für Chirurgische Forschung

Involved external institutions

Houston Texas Medical Center US United States (USA) (US) University of Glasgow GB United Kingdom (GB) Johns Hopkins University (JHU) US United States (USA) (US) Technische Universität Dresden DE Germany (DE) University of Texas MD Anderson Cancer Center US United States (USA) (US) University of Queensland AU Australia (AU) University of Sydney (USYD) AU Australia (AU) Garvan Institute of Medical Research AU Australia (AU)

How to cite

APA:

Gingras, M.-C., Covington, K.R., Chang, D.K., Donehower, L.A., Gill, A.J., Ittmann, M.M.,... Pilarsky, C. (2016). Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation. Cell Reports, 14(4), 907-19. https://doi.org/10.1016/j.celrep.2015.12.005

MLA:

Gingras, Marie-Claude, et al. "Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation." Cell Reports 14.4 (2016): 907-19.

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