Characterization of tumor mutation burden (TMB) and microsatellite instability (MSI) interplay for gastroesophageal adenocarcinoma (GA) and colorectal carcinoma (CRC).

22Background: Tumor genomic instability is positively correlated with immunotherapy response. It confers different tumor phenotypes, including high TMB (TMB-H) and high MSI (MSI-H). Recently the US Food and Drug Administration approved MSI-H phenotype as a biomarker for immunotherapy, highlighting its importance, but also bringing up the question of how TMB as another promising biomarker is going to add value in the field. Here, we characterized TMB and MSI profiles to better understand the potential TMB contribution and identify genomic markers for it. Methods: 734 solid tumor were collected, with 462 CRC, and 272 GA samples. Large panel Next-Generation Sequencing assay with the ability to determine TMB and MSI, was performed on each sample. Based on the TMB and MSI status, patients were grouped into four categories: THMH (TMB-H and MSI-H), THMS (TMB-H and MSI-Stable), TLMH (TMB-Low and MSI-H), and TLMS (TMB-Low and MSI-Stable). To identify genes that are related to the interplay of TMB and MSI, Random F...