IOF-HB/07/049.

Exploration of the MSMB methylome as a novel molecular biomarker for prostate cancer The Prostate secretory protein of 94 amino acids (PSP94), encoded by the highly prostate-specific MSMB gene, is one of the three major proteins secreted in the seminal fluid, together with PSA and Prostatic Acid Phosphatase (PAP). In advanced stages of prostate cancer the synthesis of PSP94 is lost due to epigenetic modifications of MSMB, the gene encoding PSP94. We have shown that at least a part of the CpG island, located 3 kb upstream of the transcriptional start site of the MSMB gene, is hypermethylated in the androgen-refractory prostate cancer cells (PC-3) as compared to its methylation status in the androgen-sensitive prostate cancer cells (LNCaP) and that this is associated with silencing of the MSMB gene. These results suggest that hypermethylation of this CpG island is indicative for the presence of prostate cancer. The research to perform is outlined below: 1. In-depth analysis of the methylation status of the CpG island of the MSMB promoter in four different prostate-derived cell lines by bisulphite sequencing. 2. Optimalization of the MSMB-methylome specific qMSP (quantitative Methylation-specific PCR) assay. 3. Extension of the analysis on prostate tumor samples (benign versus PrCa; indolent versus malignant PrCa) obtained from OncoMethylome Sciences. If the degree of methylation of the MSMB-promoter CpG island is associated with prostate cancer, the use of the MSMB-methylome as biomarker for prostate cancer detection becomes an attainable goal.

Trefwoorden:Biochemical