Identification of novel mutations by exome sequencing in African American colorectal cancer patients.

BACKGROUNDThe purpose of this study was to identify genome-wide single nucleotide variants and mutations in African American patients with colorectal cancer (CRC). There is a need of such studies in African Americans, because they display a higher incidence of aggressive CRC tumors. METHODSWe performed whole exome sequencing (WES) on DNA from 12 normal/tumor pairs of African American CRC patient tissues. Data analysis was performed using the software package GATK (Genome Analysis Tool Kit). Normative population databases (eg, 1000 Genomes SNP database, dbSNP, and HapMap) were used for comparison. Variants were annotated using analysis of variance and were validated via Sanger sequencing. RESULTSWe identified somatic mutations in genes that are known targets in CRC such as APC, BRAF, KRAS, and PIK3CA. We detected novel alterations in the Wnt pathway gene, APC, within its exon 15, of which mutations are highly associated with CRC. CONCLUSIONSThis WES study in African American patients with CRC provides insight into the identification of novel somatic mutations in APC. Our data suggest an association between specific mutations in the Wnt signaling pathway and an increased risk of CRC. The analysis of the pathogenicity of these novel variants may shed light on the aggressive nature of CRC in African Americans. Cancer 2015;121:34-42. (c) 2014 American Cancer Society. We have little knowledge of the phenotypic genetic changes of colorectal cancer in African Americans and their correlation with the DNA changes found in the majority of cancers in this population. Identifying biomarkers in colorectal cancer in African Americans is likely to help determine the key genes involved in the progression of this disease and identify biomarkers for targeted therapy and management in African Americans with colorectal cancer.