What question did this study set out to answer?

The aim is to characterize the molecular features of gastric adenocarcinomas in Latino patients to inform targeted therapies.

April 5, 2026

Abstract 7275: Molecular characterization of Latino gastric adenocarcinomas identifies homologous recombination deficiency and TGF-beta pathways as targets for aggressive genomically stable tumors

Key Points

The aim is to characterize the molecular features of gastric adenocarcinomas in Latino patients to inform targeted therapies.
Analyzed 192 gastric adenocarcinoma tumors from Latino patients using low-pass whole-genome sequencing or whole-exome sequencing.
Classified molecular subtypes and assessed somatic alterations compared to a non-Latino White cohort from TCGA.
Examined the frequency of specific mutations and their relationship with patient ancestry.
57.8% of tumors were classified as genomically stable (GS), significantly higher than the 11.5% in the NLW cohort.
Frequent mutations were found in genes related to the cadherin/catenin complex and DNA damage repair.
65% of GS tumors lacked therapeutically actionable biomarkers, but ATM mutations indicate potential for PARP inhibitors.

Abstract

Abstract Background: Gastric cancer (GC) disproportionately affects Latino populations, yet genomic data from these patients remain scarce. This underrepresentation limits understanding of ancestry-specific molecular features that could inform targeted therapies. Tumors characterized by a genomically stable (GS) subtype are associated with worse outcomes and is more prevalent among Asians and Hispanics than among non-Latino White (NLW) and Black populations. Methods: We analyzed 192 gastric adenocarcinoma tumors from Latino patients (Colombia, Mexico, and U.S.) using low-pass whole-genome sequencing (LP-WGS), or whole-exome sequencing. Molecular subtypes were classified, and somatic alterations were assessed and compared to the NLW cohort from the cancer genome atlas (TCGA). Results: Similar to previous studies, the GS subtype was predominant (57.8%) in this Latino cohort, significantly higher than the mostly NLW, TCGA-STAD (11.5%, p 10-29). GS tumors had frequent alterations in cadherin/catenin complex genes (CDH1, CTNND1) as well as the DNA damage repair gene ATM, and TGF-β related pathway members TGFBR2 and ELF3. We identified six novel significantly mutated genes in non-hypermutated tumors and subtype-specific drivers that differ in frequency based on self-identified race. Comparative analysis revealed genetic ancestry-linked differences, including greater Indigenous American (IA) ancestry in diffuse histology tumors and higher CDH1 mutation frequency. Analysis of the therapeutically actionable biomarkers were limited in GS tumors (65% lacked targets), but ATM mutations suggest potential benefit from PARP inhibitors. Conclusions: Latino GC tumors are enriched for GS subtype and harbor unique genomic alterations, including novel drivers and HRR pathway defects. These findings underscore the need for ancestry-informed therapeutic strategies and highlight PARP inhibition as a promising avenue for GS tumors. Citation Format: Dennis J. Montoya, Ana Patricia Estrada-Florez, Paul Lott, Katherine Chiu, Javi Villalpando, Shriveda Reddy, Jasmine Diaz Sezati, Fabian Castro, Guadalupe M Polanco-Echeverry, Magdalena Echeverry de Polanco, Javier Torres, Mabel Bohorquez, Luis G. Carvajal-Carmona. Molecular characterization of Latino gastric adenocarcinomas identifies homologous recombination deficiency and TGF-beta pathways as targets for aggressive genomically stable tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7275.

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Cite This Study

Montoya et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fd73a79560c99a0a384c https://doi.org/https://doi.org/10.1158/1538-7445.am2026-7275

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