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

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

Aldo Scarpa;Rita T. Lawlor;Stefania Beghelli;Vincenzo Corbo;Maria Scardoni;Claudio Bassi
2016-01-01

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 beta-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis.
Adenocarcinoma; Ampulla of Vater; Base Sequence; DNA-Binding Proteins; Duodenal Neoplasms; Genomic Instability; Humans; Microsatellite Repeats; Molecular Sequence Data; Pancreatic Neoplasms; Proto-Oncogene Proteins c-ets; Transcription Factors; Mutation; Wnt Signaling Pathway
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/977315
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