Title | Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Gingras, M-C, 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 |
Corporate Authors | Australian Pancreatic Cancer Genome Initiative |
Journal | Cell Rep |
Volume | 14 |
Issue | 4 |
Pagination | 907-919 |
Date Published | 2016 Feb 02 |
ISSN | 2211-1247 |
Keywords | Adenocarcinoma, Ampulla of Vater, Base Sequence, DNA-Binding Proteins, Duodenal Neoplasms, Genomic Instability, Humans, Microsatellite Repeats, Molecular Sequence Data, Mutation, Pancreatic Neoplasms, Proto-Oncogene Proteins c-ets, Transcription Factors, Wnt Signaling Pathway |
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. |
DOI | 10.1016/j.celrep.2015.12.005 |
Alternate Journal | Cell Rep |
PubMed ID | 26804919 |
PubMed Central ID | PMC4982376 |
Grant List | P50 CA062924 / CA / NCI NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States FLF2015_04_GLASGOW / PANCREATICCANUK_ / Pancreatic Cancer UK / United Kingdom C29717/A17263 / CRUK_ / Cancer Research UK / United Kingdom P30 CA125123 / CA / NCI NIH HHS / United States C596/A18076 / CRUK_ / Cancer Research UK / United Kingdom HG003273 / HG / NHGRI NIH HHS / United States 17263 / CRUK_ / Cancer Research UK / United Kingdom |
Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation.
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