814 SMAD4 AS A POTENTIAL GATEKEEPER FOR GENOMIC INSTABILITY AND MTOR-MEDIATED TUMORIGENESIS IN ESOPHAGEAL ADENOCARCINOMA

Abstract

Abstract   Extensive genomic analysis of patient samples has identified genes whose mutation or loss map malignant progression from Barrett’s metaplasia, through low- (CDKN2A) and high-grade dysplasia (TP53), to invasive adenocarcinoma (SMAD4). Interestingly, loss of SMAD4 has been found to occur exclusively in the invasive disease stage, but the reason for this is unknown. This work aimed to characterise the role of SMAD4 in esophageal adenocarcinoma (EAC) tumorigenesis and identify novel therapeutic targets for SMAD4-deficient EAC. Methods We developed a novel in vivo tum..