Profile methyla tion in penile carcinoma

Abstract

Penile cancer has a low incidence in the world with the highest rates being reported in Brazil and Africa. The predominant histological subtype is squamous cell carcinoma, representing over 95% of cases. Among the risk factors that predispose to the development of this disease are reported the presence of foreskin, precarious hygiene habits and HPV infection. Despite of unpredictable behavior, high morbidity and mortality, and aggressive treatment (mutilated disease), there are only few data on the molecular and epigenetic mechanisms involved in this disease. Epigenetic changes are heritable traits that include reversible covalent modification of histone proteins and DNA methylation. The process of CpGs islands methylation has been linked to inactivation of tumor suppressor genes and plays a critical role in the development and progression of cancer. This study will assess the differential methylation profile of normal and tumor penile samples, by using a microarray platform containing approximately 27,000 islands CpGs associated with promoter regions (CpG Island platform Human Chip-on-Chip 244K - Agilent Technologies). The use of large-scale methodologies to characterize methylated and unmethylated CpGs islands in normal and tumor tissue is vital to the discovery of markers that can contribute to understanding the role of DNA methylation in neoplastic development and progression. The study data will be compared with the pattern of genomic changes by CGH-array, gene expression in large scale by oligoarrays and in relation to the HPV genotypes, obtained from other studies of the group. The aim of the present study is to identify molecular markers that may contribute to the knowledge of the biology of these tumors poorly characterized. (AU)