Ampullary cancers harbor the tumor suppressor gene ELF3 and exhibit frequent WNT Dysregulation

Gingras, Marie-Claude, Covington, Kyle R., Chang, David K., Donehower, Lawrence A., Gill, Anthony J., Ittmann, Michael M., Creighton, Chad J., Johns, Amber L., Shinbrot, Eve, Dewal, Ninad, Fisher, William E., Pilarsky, Christian, Grutzmann, Robert, Overman, Michael J., Jamieson, Nigel B., Van Buren II, George, Drummond, Jennifer, Walker, Kimberly, Hampton, Oliver A., Xi, Liu, Muzny, Donna M., Doddapaneni, Harsha, Lee, Sandra L., Bellair, Michelle, Hu, Jianhong, Han, Yi, Dinh, Huyrn H., Dahdouli, Mike, Samra, Jaswinder S., Bailey, Peter, Waddell, Nicola, Pearson, John V., Harliwong, Ivon, Wang, Huamin, Aust, Daniela, Oien, Karin A., Hruban, Ralph H., Hodges, Sally E., McElhany, Amy, Saengboonmee, Charupong, Duthie, Fraser R., Grimmond, Sean M., Biankin, Andrew V., Wheeler, David A. and Gibbs, Richard A. (2016) Ampullary cancers harbor the tumor suppressor gene ELF3 and exhibit frequent WNT Dysregulation. Cell Reports, 14 4: 907-919. doi:10.1016/j.celrep.2015.12.005

Author Gingras, Marie-Claude
Covington, Kyle R.
Chang, David K.
Donehower, Lawrence A.
Gill, Anthony J.
Ittmann, Michael M.
Creighton, Chad J.
Johns, Amber L.
Shinbrot, Eve
Dewal, Ninad
Fisher, William E.
Pilarsky, Christian
Grutzmann, Robert
Overman, Michael J.
Jamieson, Nigel B.
Van Buren II, George
Drummond, Jennifer
Walker, Kimberly
Hampton, Oliver A.
Xi, Liu
Muzny, Donna M.
Doddapaneni, Harsha
Lee, Sandra L.
Bellair, Michelle
Hu, Jianhong
Han, Yi
Dinh, Huyrn H.
Dahdouli, Mike
Samra, Jaswinder S.
Bailey, Peter
Waddell, Nicola
Pearson, John V.
Harliwong, Ivon
Wang, Huamin
Aust, Daniela
Oien, Karin A.
Hruban, Ralph H.
Hodges, Sally E.
McElhany, Amy
Saengboonmee, Charupong
Duthie, Fraser R.
Grimmond, Sean M.
Biankin, Andrew V.
Wheeler, David A.
Gibbs, Richard A.
Title Ampullary cancers harbor the tumor suppressor gene ELF3 and exhibit frequent WNT Dysregulation
Formatted title
Ampullary cancers harbor the tumor suppressor gene ELF3 and exhibit frequent WNT Dysregulation
Journal name Cell Reports   Check publisher's open access policy
ISSN 2211-1247
Publication date 2016-02-02
Sub-type Article (original research)
DOI 10.1016/j.celrep.2015.12.005
Open Access Status DOI
Volume 14
Issue 4
Start page 907
End page 919
Total pages 14
Place of publication New York, NY, United States
Publisher Elsevier
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
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.
Keyword General Biochemistry, Genetics and Molecular Biology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID P50 CA062924
U54 HG003273
P30 CA125123
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
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