Epigenetic markers for molecular detection of prostate cancer

Issue title: Epigenetic Markers

Article type: Research Article

Authors: Costa, Vera L. | Henrique, Rui^; | Jerónimo, Carmen^{; ;}

Affiliations: Department of Genetics, Portuguese Oncology Institute – Porto, Rua Dr. Antonio Bernardino de Almeida, 4200-072 Porto, Portugal | Department of Pathology, Portuguese Oncology Institute – Porto, Rua Dr. Antonio Bernardino de Almeida, 4200-072 Porto, Portugal | Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal | Fernando Pessoa University School of Health Sciences, Rua Carlos da Maia, 296, 4200-150, Porto, Portugal

Note: [] Corresponding author: Dr. Carmen Jerónimo, Department of Genetics, Portuguese Oncology Institute – Porto, Rua Dr. Antonio Bernardino de Almeida, 4200-072 Porto, Portugal. Tel.: +351 225084000 (ext. 5610); Fax: +351 225084016; E-mail: [email protected]

Abstract: Prostate cancer is a highly prevalent malignancy, which is clinically silent but curable while organ-confined. Because available screening methods show poor sensitivity and specificity, the development of new molecular markers is warranted. Epigenetic alterations, mainly promoter hypermethylation of cancer-related genes, are common events in prostate cancer and might be used as cancer biomarkers. Moreover, the development of quantitative, high-throughput techniques to assess promoter methylation enabled the simultaneous screening of multiple clinical samples. From the numerous cancer-related genes hypermethylated in prostate cancer only a few proved to be strong candidates to become routine biomarkers. This small set of genes includes GSTP1, APC, RARβ2, Cyclin D2, MDR1, and PTGS2. Single and/or multigene analyses demonstrated the feasibility of detecting early prostate cancer, with high sensitivity and specificity, in body fluids (serum, plasma, urine, and ejaculates) and tissue samples. In addition, quantitative hypermethylation of several genes has been associated with clinicopathologic features of tumor aggressiveness, and also reported as independent prognostic factor for relapse. The identification of age-related methylation at specific loci and the differential frequency of methylation among ethnical groups, also provided interesting data linking methylation and prostate cancer risk. Although large trials are needed to validate these findings, the clinical use of these markers might be envisaged for the near future.

Keywords: Prostate cancer, epigenetics, methylation, molecular markers, biomarkers

Journal: Disease Markers, vol. 23, no. 1-2, pp. 31-41, 2007