Abstract 3616: Somatic mutation profiling of colorectal cancer by targeted next generation sequencing

Aim: This study aimed to sequence custom 96 genes of tumor suppressor genes and oncogenes frequently associated with colorectal cancer (CRC) to identify the frequency of the detected genetic mutations in the disease progression of CRC patients and to develop personalized therapy in those somatic mutation carriers. Material and methods: Biopsy samples were collected from Egyptian patients classified into inflammatory bowel disease (IBD) (n=20), colonic polyp (CP) (n=38) and CRC (n=60) patients as well as subjects with chronic non-specific 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 with an average coverage of 500x were annotated against Cosmic and dbSNP and Clinvar databases. Results: Analysis revealed that 52 genes harbor 128, 47 genes harbor 111, 40 genes harbor 71 and 39 genes harbor 66 somatic variants were detected in the CRC, CP, IBD and control groups; respectively. ARID1A (c.5548dupG (5%)), ATM (c.2572T>C (10%)), AXIN2 (c.1975C>T (5%)), FLCN (c.1285dupC (8%)), KRAS (c.35G>T (8%)), MSH6 (c.3261dupC (5%)), SLC9A9 (c.1765A>G (10%)), TP53 (c.1024C>T (5%)) were found to be the highly frequently detected pathogenic CRC specific variants. We also identified 29 genes harbor 43 common variants. The highly frequently common detected variants were ACVR2A (c.1310delA), ATM (c.5557G>A), BRCA1 (c.3548A>G, c.2612C>T), BRCA2 (c.1114A>C), IGF2 (c.677delG), KIT (c.1621A>C), MLH1 (c.655A>G), MLK4 (c.2223G>T, c.2182G>A), PIK3CA (c.1173A>G), PTPN12 (c.964G>A), RET (c.2071G>A), TP53 (c.121delG, c.215C>G) Conclusion: Our data showed that our Egyptian genetic makeup is different from other population. Also, the identified somatic mutations are crucial for understanding cancer predisposition and developing personalized therapies for the Egyptian colorectal cancer patients. Citation Format: Amira Salah El-Din Youssef, Ahmed Moustafa, Ahmed Osama Touny, Zeinab K. Hassan, Mohammed Mohey Eldin, Mai M. Lotfy, Auhood Nassar, ola sayed, Abdel-Rahman N. Zekri. Somatic mutation profiling of colorectal cancer by targeted next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3616.