A mutational co-occurrence network in gastric cancer based on an association index

Abstract

Gastric cancer (GC) is one of the most lethal, as well as one of the heterogeneous, cancer types. Possible GC molecular mechanisms could be revealed by mutational co-occurrence analyses. Despite a known association between mutational co-occurrences and GC signalling contexts, no specific mechanisms have been identified. Here, known GC signalling contexts, including cancer hallmarks (DNA repair, WNT signalling, Notch signalling), were inspected in terms of mutational co-occurrences, and in particular, for a specific GC phenotype, microsatellite status (stable or low or high instability). By correlating mutational co-occurrences of gene pairs within cancer hallmarks, we constructed mutational co-occurring networks for each type of microsatellite status. As a result, we found that one status type, microsatellite-stable (MSS), associated with mutation of JAG1, likely co-occurs for genes belonging to the WNT and Notch signalling pathways. Our study may support the feasibility of a new therapeutic strategy of designing compounds that target Notch signalling, in MSS GC patients.