Prostate cancer is the most commonly diagnosed non-skin cancer in most western countries. Family history is well established as a clear risk factor for prostate cancer, as demonstrated by twin and familial studies. However, despite major efforts and multiple linkage studies, only a few genetic changes have been identified that confer susceptibility to prostate cancer, which explain only a minority of the families. Given the complexity of hereditary prostate cancer, novel approaches complementary to the traditional approach of linkage analysis, are needed to assist with gene identification in prostate cancer. We propose to use array based comparative genomic hybridization (aCGH) in prostate cancers from hereditary families to further the identification of genes important in hereditary prostate cancer, in collaboration with members of the International Consortium for Prostate Cancer Genetics.
In Specific Aim 1, we will characterize the chromosomal amplifications and deletions in prostate cancers from hereditary prostate families using Acgh and correlate the findings with previously identified regions of linkage.
In Specific Aim 2, we will determine if there are common regions of chromosomal loss or gain shared between family members suggesting the locus of a shared genetic change. As an exploratory aim, we will perform cluster analyses on the aCGH data to explore whether we can differentiate between families using tumor profiles, and thus decrease the genetic heterogeneity in prostate cancer linkage studies. Together these aims represent a significant step forward in the effort to identify prostate cancer susceptibility genes. In addition, they will provide important information about somatic chromosomal amplifications and deletions in prostate cancer development on a scale not previously achievable. Identifying genes in hereditary prostate cancer will provide important insights into genetic variation and biology associated with prostate cancer development both in high-risk cases and the general population, furthering our ability to predict who is at highest risk of prostate cancer. ? ?
