title: Novel recurrently mutated genes in African American colon cancers.
abstract: We used whole-exome and targeted sequencing to characterize somatic mutations in 103 colorectal cancers (CRC) from African Americans, identifying 20 new genes as significantly mutated in CRC. Resequencing 129 Caucasian derived CRCs confirmed a 15-gene set as a preferential target for mutations in African American CRCs. Two predominant genes, ephrin type A receptor 6 (EPHA6) and folliculin (FLCN), with mutations exclusive to African American CRCs, are by genetic and biological criteria highly likely African American CRC driver genes. These previously unsuspected differences in the mutational landscapes of CRCs arising among individuals of different ethnicities have potential to impact on broader disparities in cancer behaviors.
authors.affiliation: Division of General Medical Sciences-Oncology, Case Comprehensive Cancer Center, and Department of Medicine.
authors.forename: Kishore
authors.initials: K
authors.lastname: Guda
authors.affiliation: Case Comprehensive Cancer Center, and Department of Medicine.
authors.forename: Martina L
authors.initials: ML
authors.lastname: Veigl
authors.affiliation: Division of General Medical Sciences-Oncology, Case Comprehensive Cancer Center, and.
authors.forename: Vinay
authors.initials: V
authors.lastname: Varadan
authors.affiliation: Division of Hematology and Oncology.
authors.forename: Arman
authors.initials: A
authors.lastname: Nosrati
authors.affiliation: Division of Hematology and Oncology.
authors.forename: Lakshmeswari
authors.initials: L
authors.lastname: Ravi
authors.affiliation: Division of Hematology and Oncology.
authors.forename: James
authors.initials: J
authors.lastname: Lutterbaugh
authors.affiliation: Division of Hematology and Oncology.
authors.forename: Lydia
authors.initials: L
authors.lastname: Beard
authors.affiliation: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390; and.
authors.forename: James K V
authors.initials: JK
authors.lastname: Willson
authors.affiliation: Case Comprehensive Cancer Center, and Department of Medicine, Division of Hematology and Oncology.
authors.forename: W David
authors.initials: WD
authors.lastname: Sedwick
authors.affiliation: Case Comprehensive Cancer Center, and Department of Genetics and Genome Sciences.
authors.forename: Zhenghe John
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department of Genetics and Genome Sciences.
authors.forename: Neil
authors.initials: N
authors.lastname: Molyneaux
authors.affiliation: Department of Genetics and Genome Sciences.
authors.forename: Alexander
authors.initials: A
authors.lastname: Miron
authors.affiliation: J. Craig Venter Institute, La Jolla, CA 92037.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Adams
authors.affiliation: Case Comprehensive Cancer Center, and Department of Epidemiology and Biostatistics.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
authors.affiliation: Case Comprehensive Cancer Center, and Department of Medicine, Division of Hematology and Oncology, Case Medical Center, Case Western Reserve University, Cleveland, OH 44106; sxm10@cwru.edu.
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
authors.affiliation: Case Comprehensive Cancer Center, and Department of Medicine, Case Medical Center, Case Western Reserve University, Cleveland, OH 44106; Department of Pathology.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Willis
mesh_terms: D001741:Black or African American / Q000235:genetics*; D003110:Colonic Neoplasms / Q000208:ethnology* / Q000235:genetics*; D059472:Exome; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D036124:Receptor, EphA6 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D036124:Receptor, EphA6
keywords: African American; Caucasian; colon cancer; mutation; next-generation sequencing