Abstract
Background: Colorectal cancer (CRC) incidence is progressively increasing in Egypt. Unfortunately, there is inadequate knowledge of the acquired somatic mutations in Egyptian CRC patients which limit our understanding of its progression. To the best of our knowledge, our study is the first to sequence multiple-gene panel to identify the somatic mutation pattern associated with CRC disease progression in a cohort of Egyptian patients. Custom 72 genes, which are frequently associated with CRC, were sequenced using Qiaseq UMI-based targeted DNA panel in 120 fresh tissues classified into; inflammatory bowel disease (IBD; n=20), colonic polyp (CP; n=38) and CRC (n=62) as well as 20 biopsies with non-specific colitis served as a control group (n=20). Results: Using Ingenuity Variant Analysis (IVA), we revealed that APC, TP53 & ATM genes harbored the highly frequent CRC-specific somatic mutations (15, 11 & 6, respectively). We also identified common somatic mutations (predictors) that were associated with disease progression from colitis to CRC; APC (c.1742delA (65%)), TP53 (c.121delG (58%), c.215C>G (52%)), ATM (c.640delT (16%)), IGF2 (c.677delG (56%)), RET (c.2071G>A (37%)), ACVR2A (c.1310delA (26%)), PIK3CA (c.1173A>G (16%)) & KIT (c.1621A>C (13%)). Furthermore, pathway analysis using Ingenuity Pathway Analysis (IPA) showed that Wnt/βcatenin, ATM signaling, RTK-RAS and TGF-β were the most altered pathways in the CRC group (73%. 72%, 40% & 36%, respectively).Conclusion: In this data set, we shed the light on the most frequent somatic mutations and the most altered pathways that are crucial for understanding colorectal cancer predisposition and developing personalized therapies for the Egyptian CRC patients.
Deep Next Generation Sequencing Identifies Somatic Mutational Signature in Egyptian Colorectal Cancer Patients
