Molecular profiles of gastric adenocarcinoma among Hispanic patients at a safety-net healthcare system.

Abstract

e16067 Background: Hispanic patients with gastric cancer are more likely to have advanced stage at diagnosis, signet ring histology, and worse survival outcomes than non-Hispanic patients. Although socioeconomic factors may contribute to these disparities, the molecular biology of gastric cancer in Hispanic patients has not been well characterized. Hispanic patients comprise < 0.05% of gastric adenocarcinoma cases in The Cancer Genome Atlas (TCGA). Methods: We conducted a retrospective study of patients with gastric adenocarcinoma diagnosed between January 2019 to January 2022 at a safety net hospital in Houston, Texas. The hospital serves a patient population of which 91% are racial/ethnic minorities and 57% are Hispanic. Next generation sequencing data was obtained via Tempus|xT tissue assay (DNA sequencing of 648 genes in tumor and matched normal samples at 500x depth) and/or Tempus|xF liquid biopsy assay (ctDNA sequencing of 105 genes in peripheral blood samples at 5,000x depth) for germline and/or somatic mutations. We compared mutation findings in Hispanic vs non-Hispanic patients. Results: Among 56 patients with gastric adenocarcinoma, 45 (80%) were Hispanic, 11 (20%) were non-Hispanic White, Black, or other, 30 (54%) were male, median age was 54±13, and 14 (25%) were younger than 50 years old. The majority were metastatic (65%), and 6 (11%) were signet ring cell subtype. The most common pathogenic somatic variants across the entire cohort included: TP53 (55%) , CDH1 (34%) , ARID1A (25%) , LRP1B (20%) , RHOA (16%) , SMAD4 (16%) , ERBB2 (14%) , KRAS (14%) , CDKN2A (12%), and PIK3CA (12%). Microsatellite instability was found in 1 (0.02%) patient. Somatic CDH1 mutations were present in 15 (33%) Hispanic patients, of whom 7 were younger than 50 years old, and 2 (18%) non-Hispanic patients. Germline CDH1 mutations was identified in 1 Hispanic patient. TP53 mutations occurred in 14 (31%) Hispanic patients and 6 (55%) non-Hispanic patients. Conclusions: CDH1 mutations, which are associated with familial gastric cancers and more aggressive disease, were present in 33% of Hispanic patients with gastric adenocarcinoma in our study. Nearly half of these identified patients were younger than 50 years old. The high frequency of CDH1 mutations may contribute to the unique pathogenesis of gastric cancers in Hispanic patients.