Are VHL, PBRM1 and SETD2 genes distinctive diagnostic markers for kidney cancer? a molecular investigation

Kidney cancer is the most lethal urological cancer and accounts for 3% of adult malignancies. Kidney cancer is not a single disease; it is made up of a number of different types including renal cell tumours as the most common type. VHL gene is a tumor suppressor, it is best known with RCC. The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC including PBRM1 and SETD2. The PBRM1 gene is the second most common mutated gene after VHL, a tumor suppressor gene. It encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes.SETD2 encodes a histone methyltransferase, which is responsible for trimethylation of the lysine residue at position 36 of histone H3 and may play a role in suppressing tumor development. In this study, 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were observed with gene expression analysis, SSCP and sequencing technique. Three of genes VHL, PBRM1 and SETD2 were relatively downregulated. However, statistically no significance found by Wilcoxon signed rank test (p>0,05). As a result of gene screening no mutation (no different genotype) was observed. In conclusion, the mRNA expression levels of three genes were insignificantly downregulated. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Keywords: Kidney cancer, VHL, PBRM1, SETD2, Expression analysis, Mutation screening