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https://hdl.handle.net/2440/116522
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Type: | Journal article |
Title: | Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation |
Author: | Gingras, M. Chang, D. Donehower, L. Covington, K. Gill, A. Ittmann, M. Creighton, C. Johns, A. Shinbrot, E. Dewal, N. Fisher, W. Pilarsky, C. Grützmann, R. Overman, M. Jamieson, N. Van Buren, G. Drummond, J. Walker, K. Hampton, O. Xi, L. et al. |
Citation: | Cell Reports, 2016; 14(4):907-919 |
Publisher: | Elsevier |
Issue Date: | 2016 |
ISSN: | 2211-1247 2211-1247 |
Statement of Responsibility: | Jing Tan, Patrick Tan and Bin Tean Teh |
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. |
Keywords: | Australian Pancreatic Cancer Genome Initiative Ampulla of Vater Humans Adenocarcinoma Duodenal Neoplasms Pancreatic Neoplasms Genomic Instability DNA-Binding Proteins Transcription Factors Base Sequence Microsatellite Repeats Mutation Molecular Sequence Data Proto-Oncogene Proteins c-ets Wnt Signaling Pathway |
Rights: | © 2016 Elsevier Inc. |
DOI: | 10.1016/j.celrep.2015.12.005 |
Published version: | http://dx.doi.org/10.1016/j.celrep.2015.12.005 |
Appears in Collections: | Aurora harvest 8 Mechanical Engineering publications |
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