# Analysis of biopsies of gastric cancer, intestinal and diffuse, and non-atrophic gastritis: an overview of loss of heterozygosity in Mexican patients

## TL;DR

This study examines loss of heterozygosity in gastric cancer and non-atrophic gastritis in Mexican patients, identifying key genes and pathways involved in cancer development.

## Contribution

The study identifies specific LOH regions and genes associated with gastric cancer subtypes and non-atrophic gastritis in a Mexican population.

## Key findings

- Chromosomes 6 and 8 are primarily affected in diffuse gastric cancer, while chromosomes 3, 16, and 17 are affected in intestinal gastric cancer.
- Five LOH-genes (IRAK1, IKBKG, PAK3, TKTL1, PRPS1) are shared between gastric cancer and non-atrophic gastritis, suggesting an early role in carcinogenesis.
- Specific genes are linked to cancer hallmarks like genomic instability, metastasis, and immune evasion in different gastric cancer subtypes.

## Abstract

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).