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Abstract:
There is abundant evidence to suggest that epigenetic DNA methylation changes may appear early during prostate cancer (PCa) development than genetic changes, and are more common and consistent. The purpose of this study is to investigate whether aberrant DNA methylation occurs as a function of age and if it accompanies neoplastic transformation of the human prostate. RESULTS: Using methylated CpG island amplification coupled with promoter microarray and also genome-wide DNA methylation analysis, I have identified several novel genes that are differentially methylated in normal and PCa tissues. In addition, I have also identified novel methylated patterns among preinvasive and cancerous lesions of the prostate. Quantitative methylation analysis revealed significant differences (p 0.05) in methylation level for several genes in African-American (AA) samples versus Caucasian (Cau) samples. Furthermore, regression analysis revealed significantly higher methylation for NKX2-5 (p = 0.008) and TIMP3 (p = 0.039) genes in normal prostate tissue samples from AA versus Cau, and a statistically significant association of methylation with age for NKX2-5 (p = 0.03) in AA versus Cau. In addition, functional studies demonstrate that NKX2-5 may have tumor suppressor function in PCa cells. CONCLUSION: I have identified several novel methylated genes as potential (ethnic sensitive) biomarkers for early disease detection and for distinguishing indolent from aggressive PCa.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Final rept. 1 Jun 2008-14 Jun 2011 |
| Pages: |
124 |
| Report Date: |
Jul 2011 |
| Contract Number: |
W81XWH-08-1-0372 |
| Report Number: |
A066255 |
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