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ARID1A/BAF250a has been recently implicated as a tumor suppressor in gastric cancer. We sought to clarify the clinical significance of BAF250a/ARID1A in relation to other clinical parameters and relevant biomarkers in gastric carcinoma. Cases from 2 separate cohorts of patients with gastric carcinoma from Vancouver (n = 173) and Toronto (n = 80) were selected for the construction of tissue microarrays, which were used to assess the immunohistochemical status of BAF250a (anti-ARID1A), mismatch repair proteins and p53, as well as in situ hybridization for HER2 amplification and Epstein-Barr virus infection. The Toronto cohort contained a higher proportion of early stage cases (P = .019) and a smaller proportion of cases from the proximal stomach (P < .001). Overall, immunohistochemical loss of BAF250a was observed in 22.5% of gastric adenocarcinomas from the Vancouver group and 20% from Toronto. In both cohorts, loss of BAF250a was positively associated with loss of mismatch repair protein expression (P < .0001 and P = .035, respectively). Loss of BAF250a expression was independently associated with poor overall survival in the Toronto cohort (P = .0015), whereas no significant association with survival was observed in the Vancouver cohort. BAF250a loss was not significantly associated with any additional clinical parameters in either cohort. HER2 amplification was confirmed as a negative prognostic factor in both cohorts. These findings suggest that ARID1A/BAF250a may be of prognostic significance in a subset of patients with early stage gastric cancer and that pathological assessment should increasingly use a multimarker approach., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. Methods We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma. Results In the first case, genomic profiling revealed an IDH1 somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, a BRAF V600E mutation and wild-type KRAS profile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation; RAS/RAF/MEK, AKT/MTOR, Wnt, and NOTCH pathway activation; and overexpression of RET, ERBB2 (HER2), ERBB3, MET, and cell cycle regulators. Summary We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information. [ABSTRACT FROM AUTHOR]