Vol 4, No 1 (2017)

The cytoplasmic actins (β and γ) play crucial roles during key cellular processes like adhesion, migration, polarization and cytokinesis. The understanding of their specific underlying mechanisms would be of major relevance not only for fundamental research but also for clinical applications, since modulations of actin isoforms are directly or indirectly correlated with severe pathologies. The major goal of the research was to elucidate the function of the actin isoforms during motile activities, adhesions and cell division and to investigate whether their expression and/or structural organization is related to pathological function. Selective depletion of β- and γ-cytoplasmic actins allowed attributing functional diversities of β- and γ-сytoplasmic actins. β-Сytoplasmic actin plays a preferential role in contractile activities, whereas γ-cytoplasmic actin mainly participates in the formation of a submembranous network necessary for cell shape flexibility and motile activity. The roles of isoforms in regulating the integrity of adherens and tight junctions respectively were demonstrated. Unique roles of β- and γ-cytoplasmic actins in normal cells were shown. Similar results were obtained in cancer cells compared with normal epithelial cells in culture and in human pathological tissue sections of mammary gland, colon, lung and cervix. Malignant cell transformation requires changes in the ability of cells to migrate. The disruption of actin cytoskeleton and intercellular adhesions is an important component of the acquisition of invasive properties in epithelial malignancies.

There are a lot of studies that dedicated to genetic differences between the primary tumor and metastases. This becomes relevant not only for molecular biologists for understanding carcinogenesis, but also becoming increasingly important for medical oncologists, due to the possible impact on the choice of therapy for metastatic disease. In this regard, colon cancer is an interesting model for studying the heterogeneity of the primary tumor and possible clonal evolution, because we have predictive genetic markers for target therapy. In this article, we analyzed studies on the concordance of the mutation status of the genes, intratumoral heterogeneity and processes of clonal evolution in colorectal cancer.

Gliomas are the most common brain tumors. It is difficult to detect them at early stages of disease and there is a few available therapies providing significant improvement in survival. Mutations of isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) play significant role in gliomogenesis, diagnostics and selection of patient therapy. We tested the distribution of IDH1 and IDH2 mutations in gliomas of different histological types and grades of malignancy by DNA melting analysis using our protocol with a sensitivity of 5 %. The results of this assay were confirmed by conventional Sanger sequencing. IDH1/2 mutations were detected in 74 % of lower grade gliomas (II and III, World Health Organization) and in 14 % of glioblastomas (IV, World Health Organization). Mutation rate in gliomas with oligodendroglioma component were significantly higher then in other glioma types (р = 0.014). The IDH1 mutations was the most common (79 % of general mutation number). IDH1/2 mutations can induce aberrant gene methylation. Detection of methylation rate of the gene encoding for O6-methylguanine-DNA-methyltransferase (MGMT), predictive biomarker for treatment of gliomas with the alkylating agents, has demonstrated a partial association with IDH1/2 mutations. In 73 % of IDH1/2-mutant tumors MGMT promoter methylation were observed. At the same time IDH1/2 mutations were not revealed in 67 % tumors with MGMT promoter methylation. These results indicate existence of another mechanism of MGMT methylation in gliomas. Our data strong support for necessity of both markers testing when patient therapy is selected.