Abstract C095: Molecular characterization of gastric adenocarcinoma from Latinos shows homologous recombination deficiency

Abstract Latinos have a higher risk of developing gastric cancer (GC) than non-Latino Whites (NLW). Multiple studies have shown increased treatment resistance in diffuse-type cancers, which are more prevalent in Latino patients and dominated by the genomically stable (GS) genomic subtype. However, there is little genomic data from Latino gastric tumors due to the few studies targeting this minority population. Here, we attempt to rectify the disparity of genomic data by performing whole exome and/or low-coverage whole genome sequencing on tumors from 195 Latino gastric adenocarcinoma patients, from Colombia and Mexico. We also analyze 42 Latino patients from the US from a previous study. In total, we analyze tumors from 237 patients, the largest cohort of Latino gastric cancer tumors comprehensively sequenced thus far. Molecular subtyping of our cohort shows a higher proportion of tumors with a genomically stable (GS) subtype, 59%, and less with chromosomal instability (CIN), 24%, than reported in non-Latino patients from the Cancer Genome Atlas (20% and 50% respectively). Our earlier study of germline variants from Latinos, indicated a potential enrichment of variant related to homologous recombination deficiency (HRD), an important DNA repair mechanism. Focusing on this pathway, we performed HRD scoring and show that CIN tumors had the highest HRD score compared to all other subtypes. An alternative method analyzing somatic mutational patterns identified an indel mutational signature (ID6), also related to HRD, was enriched in GS tumors. Overall, these data provide a broader picture of the genomic landscape of Hispanic tumors, highlighting HRD targeting drugs as a potential treatment for both GS diffuse-types cancers particularly seen in Latinos and CIN tumors found more generally in gastric cancer. Citation Format: Dennis J Montoya, Ana Estrada-Florez, Paul Lott, Katherine Chiu, John Suarez-Olaya, Fabian Castro, Magdalena Echeverry de Polanco, Javier Torres, Mabel Bohorquez, Luis Carvajal-Carmona. Molecular characterization of gastric adenocarcinoma from Latinos shows homologous recombination deficiency abstract. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C095.