EXPRESSION PROFILES AND METHYLATION GENES IN CLEAR CELL RENAL CARCINOMA

Renal cancer (RC) is a common malignancy of the genitourinary system. Clear cell renal cell carcinoma is the most common histological type of RC. In most cases diagnosis and prognosis of clear cell renal cell carcinoma are based on the results of instrumental tests, while search for novel molecular RC markers and their characterization remain relevant. Molecular genetic abnormalities accompanied with changes in gene expression underly the RC carcinogenesis; however, diagnostic panels of the expression markers of RC are still not widely used. This review represents the results of recent research in the area of gene expression markers of RC aimed to elaborate prognostic test systems. Application of the NotI-microarray methodology allowed for identification of many novel genes associated with RC pathogenesis. The relationship of alterations of expression level and methylation of chromosome 3 genes with RC progression and metastasis has been shown. Based on this data, a  diagnostic marker system for RC have been proposed with identification of expression and methylation profiles and novel markers, that is an urgent problem in modern urologic oncology

Frequency and effects of mutations in the KRAS gene on the survival of patients after surgical treatment of intrahepatic cholangiocarcinoma

Aim. To study the effect of mutations in the KRAS gene on the clinical course of intrahepatic cholangiocellular cancer (ICC) after surgical treatment in the Russian population.Materials and methods. A molecular genetic study of tumour tissue samples from 33 patients with intrahepatic cholangiocellular cancer obtained after surgical treatment was carried out using real-time polymerase chain reaction.Results. In the Russian population, the frequency of mutations in the KRAS gene in ICC was 27%, mainly in 12 (78%), 13 (33%), 61 (55%), 117 (44%) and 146 (44%) codons of 2, 3, 4 exons. In terms of KRAS gene mutations, intrahepatic cholangiocellular cancer is characterised by a pronounced heterogeneity. As a rule, the KRAS gene demonstrates multiple mutations at several loci and co-mutations in other genes, in particular, in IDH1/IDH2, PIK3CA, NRAS and BRAF genes. KRAS gene mutations in ICC were found to be significantly more common in women. The overall survival rate was significantly higher in patients with a KRAS mutation as compared to those with the wild type of the gene. Regarding the relapse-free survival rate in the groups of patients with the mutant and wild type of the KRAS gene, no significant differences were found.Conclusion. In the Russian population, no negative association between mutations in the KRAS gene and clinical outcomes was observed

Liver Cirrhosis as the Outcome of Non-Alcoholic Fatty Liver Disease Associated with PNPLA3 Gene RS738409 Polymorphism

Relevance: Non-alcoholic fatty liver disease is the most common liver disease worldwide. Although the disease usually has a favorable, asymptomatic course, in some cases it can occur in the form of non-alcoholic steatohepatitis, and some patients may develop cirrhosis of the liver and hepatocellular carcinoma. There are more and more foreign studies proving the relationship of genetic factors with the progression of Non-alcoholic fatty liver disease. However, information about this association in the Russian Federation remains scarce.Goal of the study: to assess the prevalence of patatinlike phospholipase domain-containing protein 3 gene variants in patients with Non-alcoholic fatty liver disease-related cirrhosis of the liver in the Russian population sample and the effect of the mutation on the course of the disease.Materials and methods: We formed three groups of patients. Group I included 30 patients with Non-alcoholic fatty liver disease-related cirrhosis of the liver. Group II included 46 patients with Non-alcoholic fatty liver disease at the non-cirrhotic stage. Group III included 25 healthy volunteers. A retrospective analysis of patient history data was performed. We analyzed the results of biochemical blood tests, coagulogram, and ultrasound examination of abdominal organs from the medical records of patients in groups I and II. Patients from groups I and II were additionally examined using hepatic shear elastometry using the aixplorer multiwave ultrasound system (SuperSonic Imagine, USA). Alleles of the patatin-like phospholipase domain-containing protein 3 gene were detected using polymerase chain reaction–restriction fragment length polymorphism.Results. During the study, we obtained statistically reliable links between Non-alcoholic fatty liver disease and the presence of a mutation in the patatin-like phospholipase domain-containing protein 3 gene (RR-2.171; 95% CI: 1.131-4.170; χ2=6.730769; p=0.00948), between liver cirrhosis and the presence of a mutation in the PNPLA3 gene (RR-4.011; 95% CI: 1.558-10.324; p=0.0003), and the relationship between the frequency of occurrence of the GG genotype of the patatin-like phospholipase domaincontaining protein 3 gene with increasing the stage of liver fibrosis in the Russian population sample.Conclusion: The patatin-like phospholipase domain-containing protein 3 gene polymorphism rs738409 is a factor in the progression of Non-alcoholic fatty liver disease to high stages of fibrosis and liver cirrhosis. Detecting of this polymorphism in patients with NAFLD in Russian population may be useful for identifying high-risk groups for disease progression