title: Identification of novel mutations by exome sequencing in African American colorectal cancer patients.
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.
authors.affiliation: Department of Medicine and Cancer Center, Howard University College of Medicine, Washington, DC.
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
authors.forename: Mohammad
authors.initials: M
authors.lastname: Daremipouran
authors.forename: Joe
authors.initials: J
authors.lastname: Devaney
authors.forename: Sudhir
authors.initials: S
authors.lastname: Varma
authors.forename: Hamed
authors.initials: H
authors.lastname: Rahi
authors.forename: Edward
authors.initials: E
authors.lastname: Lee
authors.forename: Babak
authors.initials: B
authors.lastname: Shokrani
authors.forename: Russell
authors.initials: R
authors.lastname: Schwartz
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nickerson
authors.forename: Hassan
authors.initials: H
authors.lastname: Brim
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D056915:DNA Copy Number Variations; D059472:Exome; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D017422:Sequence Analysis, DNA / Q000379:methods*; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: APC; Mutation; cancer pathways; oncogene; tumor suppressors