Data from Association of Homologous Recombination–DNA Damage Response Gene Mutations with Immune Biomarkers in Gastroesophageal Cancers
Year: 2023
Type: other
Abstract: The prevalence of homologous recombination–DNA damage response (HR-DDR) genetic alterations is of therapeutic interest in gastroesophageal cancers. This study is a comprehensive assessment of HR-DDR mutation prevalence across gastroesophageal adenocarcinomas and squamous cell carcinomas. Here we investigate the association of HR-DDR mutations with known predictors for immune-checkpoint inhibition [deficiency in mismatch-repair (dMMRP), tumor mutational burden (TMB), and programmed death ligand 1 (PD-L1)]. We confirmed HR-DDR mutations are present in a subset of gastroesophageal adenocarcinomas (23%) and gastroesophageal squamous cell carcinomas (20%). Biomarker expression of dMMRP (18% vs. 1%) and TMB-high with a cutoff of ≥10 mt/MB (27% vs. 9%) was significantly more prevalent in the DDR-mutated cohort compared with the non-DDR-mutated cohort. Mean combined positive score for PD-L1 in the total adenocarcinoma cohort was significantly higher in the DDR-mutated cohort compared with the non–DDR-mutated cohort (10.1 vs. 5.8). We demonstrated that alterations in ARID1A, BRCA2, PTEN, and ATM are correlated with dMMRP, TMB-high, and increased PD-L1 expression in gastroesophageal adenocarcinomas. Our findings show that a subset of gastroesophageal tumors harbor HR-DDR mutations correlated with established immune biomarkers. By better understanding the relationship between HR-DDR mutations and immune biomarkers, we may be able to develop better immunotherapy combination strategies to target these tumors.
Institutions: Exempla Saint Joseph Hospital, Caris Life Sciences (United States), West Cancer Center, Johns Hopkins University, Sidney Kimmel Cancer Center, Sibley Memorial Hospital, Carolinas Healthcare System, Levine Cancer Institute, Georgetown University, Georgetown University Medical Center, Georgetown Lombardi Comprehensive Cancer Center, Wayne State University, The Barbara Ann Karmanos Cancer Institute, University of Southern California, USC Norris Comprehensive Cancer Center, West Virginia University, University of Colorado Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4362488643