Abstract 2411: Identification of loss of heterozygosity-associated genes linked to loss of function in Korean population through in-silico analysis

Abstract Loss of heterozygosity (LOH) is a common event in cancer development, disrupting gene and protein translation and resulting in loss of function (LOF). In terms of additional vulnerability, recent studies have suggested that investigating LOF due to LOH can be beneficial for cancer treatment. Additionally, genetic regions, including single nucleotide polymorphisms (SNP) linked to LOF caused by LOH, vary across cancer types. From this perspective, we conducted an in-silico analysis of Korean genomic data, cancer cell line data, and public genomic databases to identify genes associated with SNPs leading to LOF due to LOH. We analyzed a total of 10 million SNPs from a large cohort of 1, 496 Koreans using whole genome sequencing (WGS) data, as well as up to 9 million SNPs from 1, 007 cancer cell lines (including 129 lung, 21 stomach, and 28 colon samples) based on whole exome sequencing (WES). After filtering out rare variants, we identified 453 functional SNPs affecting protein translation in both Korean and cancer cell line data. Of these, 194 SNPs with heterozygous genotype frequencies between 0.1 and 0.9 were selected. Using copy number loss regions from the COSMIC database, we identified 39 genes associated with potential LOH-related SNPs. Finally, through the analysis of gene expression data from The Human Protein Atlas and previous studies, six LOH-associated genes linked to LOF in Koreans were identified: ADAMTS1, ANXA2, IL17RB, LPL, TUBA8, and ZNF117. Based on these six genes, we propose a list of drugs that, when used in combination, enhance the efficacy of conventional anticancer treatments. We plan to validate the effectiveness of these drugs in addressing additional vulnerabilities through in vitro experiments. While experimental validation is ongoing, we anticipate that our study will serve as a valuable resource for researchers aiming to identify population-specific LOH-associated genes using in-silico approaches. Citation Format: Sun-Woo Lee, Jae-Yoon Kim, Hyojin Heo, Seung-Woo Baek, Jee-Woo Seo, Jong-Lyul Park, Seon-Young Kim. Identification of loss of heterozygosity-associated genes linked to loss of function in Korean population through in-silico analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2411.