Association between tumor mutation burden (TMB) and MLH1, PMS2, MSH2, and MSH6 alterations in 395 microsatellite instability-high (MSI-High) gastrointestinal (GI) tumors

Abstract

Introduction: Correlation between TMB and objective response to checkpoint inhibitors has been shown. MSI-High tumors usually exhibit high TMB. Relationship between the level of TMB and alterations in the four-mismatch repair deficiency (MMR) genes in gastrointestinal tumors has not been comprehensively studied.Methods: MSI-High status was determined by examining altered microsatellite (MS) loci using NextGen sequencing (cutoff: > =46) on a 592-gene panel. TMB was calculated by enumerating somatic missense mutations. MMR protein expression was evaluated by IHC. ANOVA and chi-square tests were used for comparisons.