MOLECULAR GENETIC DISORDERS IN THE VHL GENE AND METHYLATION OF SOME SUPPRESSOR GENES IN SPORADIC CLEAR-CELL RENAL CARCINOMAS

<span>Renal carcinoma (RC) is one of ten most common malignancies in adults and an urgent problem of modern oncology. The purpose of the study was to make a molecular genetic analysis of a number of suppressor genes in RC, which was aimed at searching for and characterizing the potential markers of the disease. Two hundred and nine RC samples were examined, of them there were 192 clear-cell carcinomas. VHL gene mutations were detected by single-strand conformation polymorphism and sequence analyses while the methylation of suppressor genes was by the methylation-sensitive polymerase chain reaction. Somatic VHL mutations were determined in 35.4% of cases of clear-cell RC (CCRC). VHL gene disorders were found in 53.7% of patients with Stage 1, which counts in favor of VHL inactivation in early-stage CCRC. The methylation of the VHL, RASSF1, FHIT, and CDH1 genes was identified in 12, 56, 58.4, and 46.4% of primary tumors, respectively; that of at least one gene was in 84.1% of the samples. The hypermethylation of the RASSF1 gene was associated with late stages (p = 0.015) and the presence of metastases (p = 0.036); that of the CDH1 gene was related to the progression, invasion, and dissemination of primary tumors (p = 0.009, 0.039, and 0.002, respectively). The findings show it possible to use an analysis of abnormalities in the VHL gene and the methylation of the RASSF1 and CDH1 genes to develop a system of molecular genetic markers of RC.