Methylation of the RASSF1A tumor suppressor gene promoter. Risk factor for carcinogenesis of urological tumors

• Published in: Urologe. Ausgabe A Vol. 47; no. 9; p. 1117
• Main Authors: Serth, J, Tezval, H, Peters, I, Atschekzei, F, Rehmet, K, Jurk, S, Albrecht, K, Kuczyk, M A, Merseburger, A S
• Format: Journal Article
• Language: German
• Published: Germany 01-09-2008
• Subjects: Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - pathology; DNA Methylation - genetics; Gene Silencing; Genes, Tumor Suppressor - physiology; Humans; Kidney - pathology; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Male; Microscopy, Fluorescence; Promoter Regions, Genetic - genetics; Prostate - pathology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Risk Factors; Tumor Suppressor Proteins - genetics
• ISSN: 0340-2592
• DOI: 10.1007/s00120-008-1821-3

Molecular targets of known risk factors for the development of urological tumors, such as age, smoking, and adiposity, have not yet been elucidated. Hypermethylation of CpG islands in promoters can lead to silencing of gene expression and has frequently been detected in tumors. Age-dependent accumulation of methylation of gene promoters has been observed in various normal tissues and is discussed as a common risk factor for carcinogenesis.Here we describe the RASSF1A tumor suppressor gene as exhibiting an age-dependent promoter methylation in normal kidney tissue, which is additionally affected by the risk factors of anthracosis and adiposity. Furthermore, we found significantly increased methylation of the RASSF1A promoter when comparing peripheral versus central zone prostatic tissue samples.Preliminary expression analysis indicates that RASSF1A could be involved in early tumorigenesis. Our results support the hypothesis that age and other lifestyle-dependent factors may influence promoter methylation of specific genes, possibly serving as future individual tumor risk markers.