222 INHERITED MITOCHONDRIAL GENE COI MUTATIONS IN PROSTATE CANCER PATIENTS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2010222 INHERITED MITOCHONDRIAL GENE COI MUTATIONS IN PROSTATE CANCER PATIENTS Takara Scott, Rebecca Arnold, Nicole Johnson, Fray Marshall, and John Petros Takara ScottTakara Scott More articles by this author , Rebecca ArnoldRebecca Arnold More articles by this author , Nicole JohnsonNicole Johnson More articles by this author , Fray MarshallFray Marshall More articles by this author , and John PetrosJohn Petros More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.280AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Mitochondrial DNA (mtDNA) gene mutations have been described in every solid adult tumor including prostate. In addition, specific inherited mtDNA haplotypes predispose individuals to the development of prostate cancer. There are marked racial differences in the specific inherited mutations within one specific gene (cytochrome oxidase 1 [COI]) in prostate cancer (PNAS 102:719-724, 2005; Prostate 69:956-60, 2009). We therefore sequenced COI genes in prostate cancer patients and compared them to published findings in diverse racial groups. METHODS Patients were prospectively enrolled in tissue and specimen banking prior to planned radical prostatectomy and peripheral blood mononuclear cell DNA prepared and stored. This DNA was used to determine inherited COI gene sequence in 293 prostate cancer patients and sequence was compared to the reference (Cambridge) sequence. All bases that differed from the reference sequence were classified as either silent or missense depending upon whether the alteration resulted in an amino acid substitution. The compiled alterations were then compared to published reports of mutations in this gene in both white and black Americans. RESULTS There is at least one base alteration (compared to the reference (revised) Cambridge sequence) in 223 out of 293 patients with prostate cancer. These 223 individuals had alterations in 90 distinct DNA bases of the COI gene (total COI bases = 1542). The majority of these alterations were silent. A total of 45 patients exhibited at least one missense mutation in this gene at 18 distinct loci. 7 missense alterations occurred in more than one patient and 11 missense mutations occurred in a single patient each. Our population of both black and white men exhibited missense mutations (e.g. T6253C, A6663G, A7146G, and T7389C) previously described in both blacks and whites. CONCLUSIONS Inherited missense mutations in the mitochondrially encoded COI gene are found in 15% of patients with prostate cancer. This is substantially higher than the rate found in individuals without prostate cancer (∼2%) and the rate found in large (disease status unknown) populations (∼8%). There appears to be prostate cancer-associated mutational “hotspots” in this gene, especially in bases that alter the amino acid sequence (missense). Blacks and whites with prostate cancer exhibit race-specific as well as race-independent mutations in COI. Further evaluation of this gene and these mutations may allow for the identification of genetically at-risk populations and provide a focus to mechanistic oriented research in prostate cancer. Atlanta, GA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e87 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takara Scott More articles by this author Rebecca Arnold More articles by this author Nicole Johnson More articles by this author Fray Marshall More articles by this author John Petros More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...