Abstract A107: Molecular subtyping of gastroesophageal junction and gastric adenocarcinomas from American Hispanic/Latino patients

Abstract

Abstract Hispanics/Latinos in the U.S. have higher incidence and mortality from gastric cancer as compared to non-Hispanic Whites. However, few Hispanic/Latino patients have been included in basic science or clinical studies in gastric cancer We analyzed information from the National Cancer Database and found that compared to Asian and White patients, Hispanics/Latino patients with gastroesophageal junction (GEJ) or gastric adenocarcinomas had a higher proportion of Stage 3 or 4 disease (64% of Hispanic/Latino patients, 58% of White patients and 54% of Asians (P < 0.001)) and were younger at the time of diagnosis (median age in years (interquartile range): Hispanic/Latino 62 (50-73), Asian: 66 (56-76), and White: 68 (59-77), P < 0.001). To determine if there were genomic factors associated with these clinical outcomes, we performed whole-exome and RNA sequencing on GEJ and GC samples from 36 Hispanic/Latino patients treated in North Texas. Using the Locating Ancestry from SEquence Reads algorithm, we analyzed the sequencing data from our cohort and the publicly available information of White and Asian patients sequenced by The Cancer Genome Atlas (TCGA) to determine ancestry. We found that each group bundled within distinct clusters. Next, we classified the tumors based on the molecular categorization scheme established by the TCGA, which defines four groups using a step-wise algorithm. Tumors are first categorized by Epstein-Barr virus (EBV) infection status and then by microsatellite instability (MSI). The remaining samples undergo somatic copy number alteration (SCNA) analysis, with high rates defining the chromosomal instability (CIN) group and low rates designating the genomically stable (GS) tumors. In our cohort of Hispanic/Latino patients, we found no EBV, two MSI (6%), ten CIN (28%), and 24 GS (66%) subtype tumors. This is a much a higher proportion of GS subtype tumors as compared to White and Asian patients sequenced by the TCGA (P < 0.001). In addition, we found a relatively high rate of germline CDH1 mutations, which are known to cause diffuse-type gastric cancer, that may explain the younger presentation age of Hispanic/Latino patients. Finally, we identified a molecular signature related to activated immune response that was prognostic for overall survival in a subset of patients. Our findings have significant clinical implications in terms of screening, genetic counseling, and treatment for Hispanic/Latino patients. Citation Format: Sam C. Wang, Yunku Yeu, Suntrea T.G. Hammer, Min Zhu, Ibrahim Nassour, Jeanne Shen, Deepak Agarwal, Scott I. Reznick, John C. Mansour, Adam C. Yopp, Hao Zhu, Tae Hyun Hwang, Matthew R. Porembka. Molecular subtyping of gastroesophageal junction and gastric adenocarcinomas from American Hispanic/Latino patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A107.