It is hypothesized that the increased incidence of advanced stage prostate cancer diagnosis for African-Americans compared with Caucasian-Americans is expressed by differing molecular genetics of tumor progression in these two ethnic groups. In our ongoing study, Comparative Genomic Hybridization was shown to be impractical as a technique to apply in a large molecular epidemiology study designed to define any ethnic-based regional DNA copy number differences during prostate cancer progression. A second technique, Fluorescence Loss of Heterozygosity, is now being tested and shows possible utility. The present proposal is designed to determine the better of two new methods for identifying regions in the tumor genome that are recurrently altered. In this study we propose to i.) assess the feasibility of performing allelic enumeration using real time quantitative fluorescence PCR analysis, called QuAAn; ii.) assess the feasibility of performing Comparative Genomic Analysis by DNA microarray analysis using oligonucleotide targets from the same regions as analyzed in specific aim number 1; iii.) compare the feasibility of these two techniques with each other and with fluorescence loss of heterozygosity, which should be completed when this proposed study begins. The experimental design for performing this project is to standardize each of the two new procedures for accurate, reproducible and systematic application; then to perform each procedure on 10 prostate tumor DNA samples from African-Americans and 10 prostate tumor DNA samples from Caucasian-Americans. Feasibility parameters such as amount of laboratory effort necessary, cost of laboratory supplies, degree of success, and total calendar time required will be determined for each procedure and used to define relative efficacy. One would envision that the best of these analysis procedures would be applicable to a large study that would subsequently be performed and provide insight into possible heritable differences that would define a genetic basis for higher incidence and mortality in African-Americans from prostate adenocarcinoma. Such a definition should allow genetic testing to provide individual risk assessment for African-American men.
| Jensen, Ronald H; Tiirikainen, Maarit; You, Liang et al. (2003) Genomic alterations in human mesothelioma including high resolution mapping of common regions of DNA loss in chromosome arm 6q. Anticancer Res 23:2281-9 |
