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.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010459-04
Application #
7292169
Study Section
(GB)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Rodriguez-Canales, J; Hanson, J C; Tangrea, M A et al. (2007) Identification of a unique epigenetic sub-microenvironment in prostate cancer. J Pathol 211:410-9
Perry, A S; Loftus, B; Moroose, R et al. (2007) In silico mining identifies IGFBP3 as a novel target of methylation in prostate cancer. Br J Cancer 96:1587-94
Perry, Antoinette S; Foley, Ruth; Woodson, Karen et al. (2006) The emerging roles of DNA methylation in the clinical management of prostate cancer. Endocr Relat Cancer 13:357-77
Hanson, Jeffrey A; Gillespie, John W; Grover, Amelia et al. (2006) Gene promoter methylation in prostate tumor-associated stromal cells. J Natl Cancer Inst 98:255-61
Grover, Amelia C; Tangrea, Michael A; Woodson, Karen G et al. (2006) Tumor-associated endothelial cells display GSTP1 and RARbeta2 promoter methylation in human prostate cancer. J Transl Med 4:13
Woodson, Karen; Gillespie, John; Hanson, Jeffrey et al. (2004) Heterogeneous gene methylation patterns among pre-invasive and cancerous lesions of the prostate: a histopathologic study of whole mount prostate specimens. Prostate 60:25-31
Woodson, Karen; Hanson, Jeffrey; Tangrea, Joseph (2004) A survey of gene-specific methylation in human prostate cancer among black and white men. Cancer Lett 205:181-8
Woodson, Karen; Hayes, Richard; Wideroff, Louise et al. (2003) Hypermethylation of GSTP1, CD44, and E-cadherin genes in prostate cancer among US Blacks and Whites. Prostate 55:199-205