Abstract PO-124: Mutational profiling of DNA repair and mismatch repair genes in the Egyptian colorectal cancer patients using targeted DNA sequencing

Abstract

Abstract Background: Colorectal cancer (CRC) remains one of the most prevalent and deadly tumor worldwide. DNA repair and mismatch repair (MMR) genes play an important role in the occurrence and development of colorectal cancer; however, there is insufficient knowledge of DNA repair and MMR mutational profile in the Egyptian Colorectal cancer (CRC) patients which limit our understanding of its progression. Aim: This study aimed to sequence DNA repair and mismatch repair (MMR) genes frequently associated with colorectal cancer (CRC) progression in order to identify their frequencies in the Egyptian CRC patients which may help in understanding colorectal carcinogenesis and developing personalized therapy. Material and methods: Biopsy samples were collected from 62 CRC Egyptian patients. The libraries were performed using Qiaseq UMI-based targeted panel and sequenced via Ion proton sequencer. The detected genetic variants with an average coverage of 500x were annotated against Cosmic and dbSNP and Clinvar databases using Ingenuity Variant analysis (IVA). Results: Regarding DNA repair genes, our results revealed that ATM & CHEK2 genes harbored 19 and 4 variants, respectively. The most frequently detected pathogenic mutations in the ATM were COSM1350741 (29%), COSM1351020 (26%) & COSM41596 (17%) while those pathogenic mutations detected in the CHEK2 were rs772683219 (2%) & rs587780181 (2%). As per MMR genes, it has been shown that MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 & PMS2 harbored 6, 6, 8, 6, 7, 3 & 4 variants, respectively. The identified pathogenic mutations in the MLH1 were COSM1131469 (32%) & rs63750217 (2%), while those pathogenic mutations detected in the MSH2 were rs63749832 (7%), COSM26124 (5%), rs63750084 (2%). Moreover, the highly frequent detected pathogenic mutations were COSM1438892 (7%) in MSH3, & rs267608093 (10%), COSM13395 (6%), COSM13394 (3%) in MSH6. Regarding PMS1, The most frequently detected pathogenic mutation was COSM1404081 (10%). However, no pathogenic mutations were detected in both PMS2 & MLH3 genes. Conclusion: In this data set, we shed the light on the most frequently identified DNA repair and MMR genetic mutations that are crucial for understanding colorectal carcinogenesis and developing ethnic-based personalized therapies in the Egyptian CRC patients. Citation Format: Amira Salah El-Din Youssef, Mai M. Lotfy, Auhood Nassar, Abdel-Rahman N. Zekri. Mutational profiling of DNA repair and mismatch repair genes in the Egyptian colorectal cancer patients using targeted DNA sequencing [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-124.