Abstract 3615: Profiling of BRCA1 & BRCA2 mutations in Egyptian colorectal cancer patients via next generation sequencing

Aim: This study aimed to sequence BRCA1 & BRCA2 genes to identify the frequency of the detected genetic mutations in the disease progression of colorectal cancer (CRC) and to estimate colorectal cancer risks in those BRCA mutation carriers. Material and methods: 140 biopsy samples were collected from Egyptian patients categorized into inflammatory bowel disease (IBD) (n=20), colonic polyp (CP) (n=38) and CRC (n=62) patients as well as subjects with chronic colitis served as a control group (n=20). The libraries were performed using Qiaseq UMI-based targeted panel and sequenced via Ion proton sequencer. The detected genetic variants at 500x were annotated against Cosmic, dbSNP, exac all, Polyphen2, Sift and Clinvar databases. Results: Analysis revealed that BRCA1 gene harbored 26, 19, 8 and 11 variants in the CRC, CP, IBD and control groups; respectively. Exon 10 was the most affected exon harbored 7 pathogenic variants in the CRC group. Two out of 7 were the most frequently detected common pathogenic variants associated with disease progression from colitis to CRC (c.1961delA (11%) & c.3214delC (16%). Moreover, 3 common begnin SNP variants were found to be related to ethnicity (c.3548A>G (58%), c.2612C>T (60%), c.4900A>G (69%). Moreover, BRCA2 gene harbored 48, 29, 24 and 18 variants in the CRC, CP, IBD and control groups respectively. Exon 2, 11, 23 were the most affected exons harbored 12 pathogenic variants in the CRC group. Four out of 12 were the most frequently detected common pathogenic variants associated with disease progression from colitis to CRC (c.3860delA (8%), c.5351delA (18%), c.9097delA (24%) & c.36delT (34%). Conclusion: Our data showed that BRCA1 & BRCA2 genes analyzed by Next-Generation Sequencing (NGS) identifies large number of pathogenic and begnin variants that are crucial for understanding CRC predisposition and early detection. Also, developing personalized therapies that efficiently target the individual CRC-specific mutations. Key words: Egyptian Colorectal cancer, BRCA1, BRCA2, pathogenic, begnin, Next Generation Sequencing Citation Format: Amira Salah El-Din Youssef, Ahmed Osama Touny, Zeinab K. Hassan, Mohammed Mohey Eldin, Mai M. Lotfy, Auhood Nassar, Mohamed El-Hadidi, Ali Kishk, ola sayed, Abdel-Rahman N. Zekri. Profiling of BRCA1 & BRCA2 mutations in Egyptian colorectal cancer patients via next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 202