Abstract 4488: Targeted sequencing revealed distinctive and pathogenic mutations in African Americans with colorectal cancer

Background & Aim: We recently analyzed 12 pairs of African American CRC tumors and their matched normal tissue using whole exome sequencing and established a panel of novel mutations that are potentially useful for the detection of CRC in this population. In this study, we examined APC, MSH3, and MSH6 mutations using targeted exome sequencing (TES) to determine distinctive mutations frequencies and their chronology in the neoplastic transformation. Materials & Methods: A total of 140 colon samples: (30 normal, 21 adenomas, 33 advanced adenomas & 56 tumors collected from African Americans were used as our discovery set on an Ion Torrent platform. A subset of 36 samples were used as validation set on an Illumina platform. Bioinformatic analysis was performed on both sets of data. Common mutations were considered validated. Results: Two novel MSH6 mutations were validated. Four known mutations in MSH3 were validated and were located in nonsynonymous (exon 10) and 1synonomous mutation (exon 18). As for the APC, 20 mutations were validated include 4 novel mutations. The novel mutations were 3 stopgain and 1 nonsynonymous located at the EB1 binding site, in the mutational cluster region (MCR), and at the 15 Amino Acid repeat. Conclusion: We here defined novel mutations that target DNA MMR and APC genes in African Americans with colorectal lesions. Greater frequency of mutations in cells defective for DNA repair and APC genes is an advantage in cell growth and genetic instability and relevant to the initiating events of colon tumorigenesis. Citation Format: Hassan Ashktorab, Hamed Azimi, Mike Nickerson, Sara Bass, Joseph Boland, Meredith Yeager, Sudhir Varma, Mohamed Daremipouran, Zaki Sherif, Shima Ghavimi, Babak Shokrani, Edward Lee, Adeyinka Laiyemo, Hassan Brim. Targeted sequencing revealed distinctive and pathogenic mutations in African Americans with colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4488.