Hypermethylation of the CpG islands in the promoter region flanking GSTP1 gene is a potential plasma DNA biomarker for detecting prostate carcinoma.

OBJECTIVES: To investigate the possibility of identifying DNA hypermethylation in the circulation of prostate cancer patients. METHODS: Plasma DNA samples were extracted from 36 prostate cancer patients and 27 benign prostate hyperplasia (BPH) cases. After extensive methylation-sensitive restriction enzyme digestion, the DNA samples were subjected to the real-time quantitative PCR amplification. Dissociation curve analysis was applied to determine if hypermethylation occurred in the promoter region flanking the GSTP1 gene, a well-documented epigenetic event among prostate cancer cells, in these plasma DNA samples. RESULTS: 11 of 36 prostate cancer patients showed positive peak pattern, indicating methylation changes occurred. Concordant data were obtained from the corresponding paraffin-embedded tissue samples available from the Tumor Bank. Twenty-five of the 27 BPH cases showed negative results, suggesting no methylation changes happened in the CpG islands in these cases. CONCLUSIONS: We have successfully identified prostate cancer genome hypermethylation in the peripheral circulation in prostate cancer patients with this protocol. This method can effectively distinguish BPH from prostate neoplasm. Although a larger number of samples are necessary to validate the capability of the protocol in practice, using plasma DNA sample is an ideal non-invasive approach for prostate neoplasm detection.

Lack of STK11 gene expression in homozygous twins with Peutz-Jeghers syndrome.

Clinical features of Peutz-Jeghers syndrome (PJS), an autosomal dominant disorder, include clusters of melanotic spots on the lips and limbs, polyposis of the gastrointestinal (GI) tract, and propensity to develop neoplasms of the GI tract, ovaries, testes, and other sites. We report twin sisters with PJS who were found to be homozygous, based on analyses of 9 DNA markers containing short tandem repeats (STR). Aberrant expression of a putative tumor suppressor gene, STK11, which encodes a serine threonine kinase, has been suggested as the etiologic factor in PJS. In both of the twin sisters with PJS, mRNA analyses by RT-PCR demonstrated a complete lack of STK11 gene expression. These results provide direct evidence that STK11 gene expression is abnormal in PJS. Detecting abnormal expression of the STK11 gene may serve as a molecular approach to the diagnosis of PJS and may facilitate genotype-phenotype correlations in PJS patients.