MicroRNAs play an important role in the regulation of expression of many genes involved in cancer pathogenesis. One of the causes of miRNA level deregulation in tumors is the methylation of CpG islands in the promoter regions of the genes that encode them. Hypermethylation may lead to the suppression of miRNA gene expression and, as a consequence, to a decrease in their inhibitory effect on target gene mRNAs. A search for new miRNA genes hypermethylated in breast cancer has been carried out in the present study. The methylation of five miRNA genes associated with breast cancer (miR-132, miR-1258, miR-107, miR-130b, miR-137) has been as studied using a representative set of 41 breast cancer samples by methylation-specific PCR. Three new genes, MIR-132, MIR-137 and MIR-1258, with a high frequency of hypermethylation (41, 37 and 34%, respectively) have been identified in breast cancer. The methylation of these genes in the breast tissues of ten donors without cancer pathology in anamnesis was only found in single cases. These results enable the involvement of three miRNAs (miR-132, miR-137, miR-1258) and the methylation of the genes that encode them in the pathogenesis of breast cancer to be suggested.

MicroRNA regulates gene expression, is involved in many cellular processes, and plays an important role in the development of cancer. The regulation of the expression of miRNA genes can be achieved by methylating their CpG islands, which is shown in different types of tumors. The methylation of miRNA genes in clear cell renal cell carcinoma (CCRCC) has mainly been studied for the miR-9 and miR-34 families. The methylation of six miRNA genes (miR-124a-2, -124a-3, -9-1, -9-3, -34b/c, -129-2) was investigated with the use of representative set of CCRCC samples (46 cases). Methylation of three genes miR-124a-2, -124a-3, and -129-2 was studied in kidney tumors for the first time. Methylation analysis was performed using methyl specific PCR. It is shown that the frequency of methylation of six genes (miR-124a-2, -124a-3, -9-1, -9-3, -34b/c and -129-2) was significantly higher in tumor samples than in samples of histologically normal tissue (P < 3 x 10(-5) by Fisher's exact test). These results suggest the properties of tumor suppressors for the six miRNA genes indicated in CCRCC. We also found correlations between the methylation frequency of some miRNA genes and signs of the progression of CCRCC (tumor size, clinical stage, loss of differentiation, and metastasis).

No abstract

Rationale: In the recent years molecular genetic prognostic factors are becoming very important for predicting the course of uveal melanoma (UM). In clinical practice, molecular genetic methods are used to identify patients with a high risk of metastases.Aim: To determine the survival of UM patients after enucleation, depending on molecular genetic aberrations.Materials and methods: Thirty (30) patients with UM aged from 23 to 83 years were examined and treated. In all cases, enucleation was performed. The removed eyes underwent morphological and molecular genetic and cytogenetic analysis (loss of heterozygocity on chromosomes 1, 3 and 8, methylation of the RASSF1A gene, mutations in GNAQ/11 genes, polymorphism of the ABCB1 gene). The median follow-up was 61 months.Results: The cumulative 3-year survival of the UM patients was 77.8 ± 8.0%, and the 5-year survival 63.0 ± 9.0%. The mean survival time was 52.8 ± 3.9 months. The patients with chromosome 3 monosomy showed significantly lower 5-year survival rates than the patients with partial monosomy and without loss of heterozygocity in chromosome 3 (log-rank test, χ2 = 14.111, p = 0.001). The loss of heterozygocity on chromosomes 1 and 8, the methylation of the RASSF1A gene, the mutations in GNAQ/11 genes, and the polymorphism of the ABCB1 gene were not associated with poorer vital prognosis.Conclusion: Molecular genetic aberrations play an important role in predicting the course of the tumor process and determining the risk of hematogenous metastasizing in UM patients. The significant role of chromosome 3 monosomy has been proved. Due to the relatively small cohort (30 patients) and the time factor (analysis of 5-year survival), the role of other molecular genetic changes has not been confirmed, which requires an assessment of not only genetic, but also clinical, echographic and morphological prognostic factors.

No abstract

No abstract

Роль метилирования генов микроРНК в различных молекулярно-биологических подтипах рака молочной железы Злокачественные опухоли www.malignanttumours.org

No abstract