Topography of tumor mutational burden (TMB) and immune-related genomic alterations (GA) across gastrointestinal malignancies (GIm): a study of 22,570 cases

摘要: Background: Response to immune checkpoint inhibitors (ICPIs) is mediated in part by tumor neoantigens. TMB has emerged as a predictive biomarker, but data is lacking in GIm. We examined TMB and concurrent GA across GIm to identify patient subsets for further study.Methods: Comprehensive genomic profiling was used to determine TMB, microsatellite instability (MSI), and additional GA using previously described methods. GA were compared among anatomically defined tumor types and stratified by TMB status (mutations/DNA megabase), and those associated with response or resistance to ICPIs were compared to identify patient subsets.Results: Median TMB was higher for tubular vs. non-tubular GIm (p= 0.032). Among the entire cohort, 3.5% and 7.4% of samples had a TMB> 20 and> 10, respectively. The proportion of tumors with TMB≥ 10 was greatest within tubular foregut structures (esophagus …