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This study analyzed the loss of heterozygosity (LOH) effect on gastric cancer (GC) tumor samples from 21 Mexican patients, including diffuse (DGC) and intestinal (IGC) subtypes, as well as non-atrophic gastritis (NAG, control). Whole-genome high-density arrays were performed, and LOH regions were identified among the tissue samples. The differences in affected chromosomes were established among groups, with chromosomes 6 and 8 primarily affected in DGC and chromosomes 3, 16, and 17 in IGC. Functional pathway analysis revealed involvement in cancer-associated processes, such as signal transduction, immune response, and cellular metabolism. Five LOH-genes (IRAK1, IKBKG, PAK3, TKTL1, PRPS1) shared between GC and NAG suggest an early role in carcinogenesis. Specific genes were highlighted for Hallmarks of Cancer NAG-related genes (PTPRJ and NDUFS) were linked to cell proliferation and growth; IGC genes (GNAI2, RHOA, MAPKAPK3, MST1R) to genomic instability, metastasis, and arrest of cell death; and DGC genes to energy metabolism and immune evasion. These findings emphasize the role of LOH in GC pathogenesis and underscore the need for further research to understand LOH-affected genes and their diagnostic or evolution potential in cancer management. Portions of this text were previously published as part of a preprint (https://www.medrxiv.org/content/10.1101/2024.07.29.24311063v1).©2025 Larios-Serrato et al.

Dra. Ruiz Tachiquín M.

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