- Title
- Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation
- Creator
- Gingras, Marie-Claude; Covington, Kyle R.; Fisher, William E.; Pilarsky, Christian; Grützmann, Robert; Overman, Michael J.; Jamieson, Nigel B.; Van Buren II, George; Drummond, Jennifer; Walker, Kimberly; Hampton, Oliver A.; Australian Pancreatic Cancer Genome Initiative,; Chang, David K.; Wong, Rachel; Donehower, Lawrence A.; Gill, Anthony J.; Ittmann, Michael M.; Creighton, Chad J.; Johns, Aamber L.; Shinbrot, Eve; Dewal, Ninad
- Relation
- NHMRC.631701 | NHMRC|535903 | NHMRC|427601
- Relation
- Cell Reports Vol. 14, Issue 4, p. 907-919
- Publisher Link
- http://dx.doi.org/10.1016/j.celrep.2015.12.005
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2016
- Description
- 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.
- Subject
- cancer; tumour suppressor; gene mutation; WNT dysregulation
- Identifier
- http://hdl.handle.net/1959.13/1323675
- Identifier
- uon:24864
- Identifier
- ISSN:2211-1247
- Rights
- This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- Language
- eng
- Full Text
- Reviewed
- Hits: 25048
- Visitors: 25792
- Downloads: 208
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 3 MB | Adobe Acrobat PDF | View Details Download |