Accession Number : ADA552660


Title :   Age-Related DNA Methylation Changes and Neoplastic Transformation of the Human Prostate


Descriptive Note : Final rept. 1 Jun 2008-14 Jun 2011


Corporate Author : HOWARD UNIV WASHINGTON DC


Personal Author(s) : Kwabi-Addo, Bernard


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a552660.pdf


Report Date : Jul 2011


Pagination or Media Count : 124


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.


Descriptors :   *AGING(PHYSIOLOGY) , *METHYLATION , *NEOPLASMS , *PROSTATE CANCER , ABNORMALITIES , DISEASES , ETHNIC GROUPS , GENES , GENETICS , PROSTATE GLAND , QUANTITATIVE ANALYSIS , REGRESSION ANALYSIS , SAMPLING , SENSITIVITY , TISSUES(BIOLOGY) , TRACER STUDIES , TRANSFORMATIONS


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE