Abstract:
BACKGROUND:The 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. METHODS:We 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. RESULTS:We 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. CONCLUSIONS:This 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.
journal_name
Cancerjournal_title
Cancerauthors
Ashktorab H,Daremipouran M,Devaney J,Varma S,Rahi H,Lee E,Shokrani B,Schwartz R,Nickerson ML,Brim Hdoi
10.1002/cncr.28922subject
Has Abstractpub_date
2015-01-01 00:00:00pages
34-42issue
1eissn
0008-543Xissn
1097-0142journal_volume
121pub_type
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