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Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):1149-54. doi: 10.1073/pnas.1417064112. Epub 2015 Jan 12.

Novel recurrently mutated genes in African American colon cancers.

Author information

1
Division of General Medical Sciences-Oncology, Case Comprehensive Cancer Center, and Department of Medicine.
2
Case Comprehensive Cancer Center, and Department of Medicine.
3
Division of General Medical Sciences-Oncology, Case Comprehensive Cancer Center, and.
4
Division of Hematology and Oncology.
5
Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390; and.
6
Case Comprehensive Cancer Center, and Department of Medicine, Division of Hematology and Oncology.
7
Case Comprehensive Cancer Center, and Department of Genetics and Genome Sciences.
8
Department of Genetics and Genome Sciences.
9
J. Craig Venter Institute, La Jolla, CA 92037.
10
Case Comprehensive Cancer Center, and Department of Epidemiology and Biostatistics.
11
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.
12
Case Comprehensive Cancer Center, and Department of Medicine, Case Medical Center, Case Western Reserve University, Cleveland, OH 44106; Department of Pathology.

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.

KEYWORDS:

African American; Caucasian; colon cancer; mutation; next-generation sequencing

PMID:
25583493
PMCID:
PMC4313860
DOI:
10.1073/pnas.1417064112
[Indexed for MEDLINE]
Free PMC Article

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