Currently, my primary research focus is in the early detection of prostate cancer using gene-specific promoter region hypermethylation. Gene hypermethylation promises to be a good early detection marker since it is a DNA-based, stable covalent modification of the DNA. My laboratory has developed assays sensitive enough to detect gene hypermethylation down to around 20 cells in a mixed pool of methylated and unmethylated DNA (can detect in a 1:10,000 ratio of methylated:unmethylated). We are able to detect tumor-specific gene methylation in serum and diagnostic biopsy samples of men with prostate cancer. We are currently initiating studies to evaluate whether evaluating methylation of a panel of genes (we are currently investigating six genes) can aid in the diagnosis of prostate cancer. The false negative rate of core-needle biopsy in the diagnosis of prostate cancer is quite high. Around 40 -50 % of men with elevated PSA levels who undergo a diagnostic biopsy are diagnosed with cancer, the other 50-60% are followed up and re-tested annually. About 20% of the men without cancer on initial biopsy go on to develop cancer within 2-5 years. We are studying whether the presence of tumor-specific gene hypermethylation in biopsy sample (and/or urine and serum) can detect the men negative for cancer on initial biopsy but subsequently develop cancer. We are also evaluating whether gene hypermethylation status can predict more aggressive disease. Of men with clinically localized prostate cancer, about 30% (depending on tumor grade and other factors) will have a recurrence. Gene methylation may predict men who may have a recurrence and these men can be treated with adjuvant therapy (they currently undergo """"""""watchful waiting""""""""). My laboratory is currently working on characterizing the methylation status of genes associated with advance stage and invasive disease.
