title: Mutational Landscape of Aggressive Prostate Tumors in African American Men.
abstract: Prostate cancer is the most frequently diagnosed and second most fatal nonskin 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 ≥7, stage ≥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 biologic significant role in the incidence and clinical outcomes of prostate cancer in African Americans. Cancer Res; 76(7); 1860-8. ©2016 AACR.
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Karla J
authors.initials: KJ
authors.lastname: Lindquist
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, California.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Paris
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California. Institute for Human Genetics, University of California San Francisco, San Francisco, California.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffmann
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Niall J
authors.initials: NJ
authors.lastname: Cardin
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Rémi
authors.initials: R
authors.lastname: Kazma
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Mefford
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, California.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Simko
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, California.
authors.forename: Vy
authors.initials: V
authors.lastname: Ngo
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan.
authors.forename: Yalei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Levin
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Chitale
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Helfand
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Rybicki
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California. Department of Urology, University of California San Francisco, San Francisco, California. Institute for Human Genetics, University of California San Francisco, San Francisco, California. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. jwitte@ucsf.edu.
authors.forename: John S
authors.initials: JS
authors.lastname: Witte
mesh_terms: D001741:Black or African American; D006801:Humans; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms / Q000473:pathology*