Somatic Mutational Landscape in Mexican Patients: CDH1 Mutations and chr20q13.33 Amplifications Are Associated with Diffuse-Type Gastric Adenocarcinoma

Abstract

The Hispanic population, compared with other ethnic groups, presents a more aggressive gastric cancer phenotype with higher frequency of diffuse-type gastric adenocarcinoma (GA); this could be related to the mutational landscape of GA in these patients. Using whole-exome sequencing, we sought to present the mutational landscape of GA from 50 Mexican patients who were treated at The Instituto Nacional de Cancerología from 2019 to 2020. We performed a comprehensive statistical analysis to explore the relationship of the genomic variants and clinical data such as tumor histology and presence of signet-ring cell, H. pylori, and EBV. We describe a potentially different mutational landscape between diffuse and intestinal GA in Mexican patients. Patients with intestinal-type GA tended to present a higher frequency of NOTCH1 mutations, copy number gains in cytobands 13.14, 10q23.33, and 12q25.1, and copy number losses in cytobands 7p12, 14q24.2, and 11q13.1; whereas patients with diffuse-type GA tended to present a high frequency of CDH1 mutations and CNV gains in cytobands 20q13.33 and 22q11.21. This is the first description of a mutational landscape of GA in Mexican patients to better understand tumorigenesis in Hispanic patients and lay the groundwork for discovering potential biomarkers and therapeutic targets.

Socioeconomic disparities and the genomic landscape of gastric cancer

“…According to the literature, it is recurrent for GI cancers to have mutations in TP53 , APC , KRAS , BRAF , and PIK3CA 34 ; however, mutation frequencies vary depending on tumor type 35 . Notably, another study conducted on a Latin-American population identified the principal somatic variants in Mexican patients with gastric adenocarcinoma also being TP53 , CDH1 , CDKN2A and ARID1A 36 . In addition, CDH1 and KMT2C have been previously linked to diffuse-type GA 37 , 38 .…”