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Identification of novel mutations by exome sequencing in African American colorectal cancer patients
Author(s) -
Ashktorab Hassan,
Daremipouran Mohammad,
Devaney Joe,
Varma Sudhir,
Rahi Hamed,
Lee Edward,
Shokrani Babak,
Schwartz Russell,
Nickerson Michael L.,
Brim Hassan
Publication year - 2015
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28922
Subject(s) - dbsnp , kras , exome sequencing , sanger sequencing , international hapmap project , exome , genetics , colorectal cancer , single nucleotide polymorphism , medicine , cancer , biology , mutation , gene , genotype
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. Cancer 2015;121:34–42 . © 2014 American Cancer Society .