Abstract 1964: The mutational pattern of cell cycle checkpoints and regulators in Egyptian colorectal cancer patients

Abstract

Abstract Background: Uncontrolled proliferation is a hallmark of cancer cells. Many cell cycle checkpoints and regulators are altered in tumors which in turn results in the accumulation of genetic aberrations. So, this study aimed to identify the mutational profile of cell cycle checkpoints and regulators in tissue biopsies in Egyptian Colorectal Cancer patients. Material and Methods: Sixty two fresh tissues samples were collected from Egyptian patients with CRC. The libraries were performed using Qiaseq UMI-based targeted panel.The detected genetic variants with an average coverage of 500x were annotated using Ingenuity Variant analysis (IVA) and pathway analysis was performed using Ingenuity Pathway analysis (IPA). Results: Data analysis revealed that TP53& ATM genes; the checkpoints at G1/S and G2/M phases, were highly mutated. They harbored 12 and 9 pathogenic mutations respectively, which cause loss of functionality. The most frequently detected pathogenic variants were c.121delG (58%) in the TP53 & c.640delT (29%) in the ATM. While CHECK2; the checkpoint at G2/M phase, harbored 4 pathogenic variants; c.430delC (16%) was the most detected one. Also, two pathogenic variants were detected in the M phase checkpoint BUB1B and the most frequently detected one was c.1669delA (37%). We also detected pathogenic variants involved in the G1/S phase regulators; SMAD4 (c.1241delT (23%)), CDKN2A (c.238delG (18%)), STK11 (c.340delG (11%)), and CDH1 (c.1955delT (19%)). Other pathogenic variants involved in G2/M phase regulators were also detected; BRCA1 (c.3214delC (16%)) & EP300 (c.4408delA (19%)). Moreover, we detected 2 pathogenic variants in M phase regulator; CDC27 (c.1998delA (7%) & c.2070delA (5%)). Conclusion: Our data showed the deregulated pattern of cell cycle checkpoints and regulators that are crucial for understanding colorectal cancer progression in Egyptian patients. Also, it may help in developing personalized targeted therapies that efficiently target the cell cycle genes mutations, thereby limits the CRC progression in those patients. Citation Format: Amira Salah El-Din Youssef, Mai M. Lotfy, Auhood Nassar, Abdel-Rahman N. Zekri. The mutational pattern of cell cycle checkpoints and regulators in Egyptian colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1964.