-Mutant Gastrointestinal Tumors Represent Heterogeneous Molecular Biology, Particularly in Microsatellite Instability, Tumor Mutation Burden, and Co-Mutated Genes: An In Silico Study.

During recent years, activating mutations in have been reported in solid tumors of various organs, and clinical trials targeting -mutant tumors have been conducted. However, no effective treatment has been established for gastrointestinal tumors targeting mutations. -mutant tumors have a higher tumor mutation burden (TMB) and microsatellite instability (MSI) than non-mutant tumors, but not all -mutant tumors are TMB- and MSI-high. Thus, a more detailed classification of -mutant tumors based on the underlying molecular mechanisms is required. Herein, we classified mutations into three groups-group 1: both mutations and amplifications; group 2: mutations annotated as putative driver mutations but without amplifications; group 3: mutations annotated as non-driver mutations (passenger mutations or unknown significance) and those that were not amplified in gastrointestinal tumors. Esophageal adenocarcinoma, gastric cancer, and colorectal cancer presented significantly higher MSI and TMB in the -mutant group than in the -wild-type group. The proportions of TMB- and MSI-high tumors and frequency of co-mutated downstream genes differed among the groups. We identified TMB- and MSI-high groups; this classification is considered important for guiding the selection of drugs for -mutant tumors with downstream genetic mutations.