Mutational landscape of aggressive prostate tumors in African American men.

Prostate cancer is the most frequently diagnosed and second most fatal non-skin cancer among men in the United States. African American men are two times more likely to develop and die of prostate cancer compared with men of other ancestries.

Previous whole genome or exome tumor sequencing studies of prostate cancer have primarily focused on men of European ancestry. In this study, we sequenced and characterized somatic mutations in aggressive (Gleason {greater than or equal to}7, stage {greater than or equal to}T2b) prostate tumors from 24 African American patients. We describe the locations and prevalence of small somatic mutations (up to 50 bases in length), copy number aberrations, and structural rearrangements in the tumor genomes compared with patient-matched normal genomes. We observed several mutation patterns consistent with previous studies, such as large copy number aberrations in chromosome 8 and complex rearrangement chains. However, TMPRSS2-ERG gene fusions and PTEN losses occurred in only 21% and 8% of the African American patients, respectively, far less common than in patients of European ancestry. We also identified mutations that appeared specific to or more common in African American patients, including a novel CDC27-OAT gene fusion occurring in 17% of patients. The genomic aberrations reported in this study warrant further investigation of their biological significance in the incidence and clinical outcomes of prostate cancer in African Americans.

Cancer research. 2016 Feb 26 [Epub ahead of print]

Karla J Lindquist, Pamela L Paris, Thomas J Hoffmann, Niall J Cardin, Remi Kazma, Joel A Mefford, Jeffrey P Simko, Vy Ngo, Yalei Chen, Albert M Levin, Dhananjay Chitale, Brian T Helfand, William J Catalona, Benjamin A Rybicki, John S Witte

Department of Epidemiology and Biostatistics, University of California San Francisco., Urology, University of California San Francisco., Department of Epidemiology and Biostatistics, Institute for Human Genetics, University of California San Francisco., Institute for Human Genetics, University of California San Francisco., Epidemiology and Biostatistics, UCSF., Epidemiology and Biostatistics, University of California San Francisco., Medical Oncology, UCSF., Urology, University of California San Francisco., Department of Public Health Sciences, Henry Ford Health System., Department of Public Health Sciences, Henry Ford Health System., Pathology, Henry Ford Hospital., Robert H. Lurie Comprehensive Cancer Center, Northwestern University., Urology, Northwestern University Feinberg School of Medicine., Department of Public Health Sciences, Henry Ford Health System., Epidemiology and Biostatistics, University of California San Francisco