Transcription factor RUNX1 is one of the key regulatory proteins in vertebrates. It controls hematopoiesis and angiogenesis. It is indispensable during embryogenesis for the emergence of sites of definitive hematopoiesis and later in mature organisms for bone marrow blood stem cells differentiation. Moreover, RUNX1 gene is a frequent target for chromosomal translocations which cause acute forms of leukemia. A lot of types of human leukemia are somehow associated with mutations in this gene. Nevertheless, to this day the precise mechanism guiding the tissue-specific manner of the RUNX1 gene expression remains unknown. In this review we tried to summarize all the experimental data accumulated during the past twenty years beginning from the date when the cDNA sequence of the RUNX1 gene was first annotated. In the first part of the review we shall focus on structure, isoforms, covalent modifications of the RUNX1 transcription factor and its participation in different regulatory cascades. In the second part we shall discuss expression regulation, mutations and chromosomal translocations of the RUNX1 gene.

In last years there is increasing interest in radiogenomics and the characterization of DNA array molecular profiles that can predict tumor and no tumor tissues radioresponse. Ongoing studies carried out worldwide in the banking of tumor and no tumor samples give evidence that perspective markers for response prediction in individual patient to intended radiation therapy can be some apoptotic indexes, spectrum a number of specific proteins, and DNA-based microarray molecular profiling analysis as well determination of single nucleotide polymorphisms in genome of the patients. So far there are only a few robust reports of molecular markers predicting tumor and no tumor tissues response to radiation. The results of new studies, which in future should be validated in larger definitive trials, are likely to see in nearest years. It is needed to determine technologies of methods and to define more precisely areas of its applications.

Individual life-time risk of melanoma in white residents of highly developed countries may be as high as 2%. Continuing rise of melanoma incidence is directly related to the improving life standards, especially to growing opportunities of attending sea resorts and getting tanned. Melanoma is usually highly aggressive and resistant to standard cytotoxic therapy, therefore 5-years survival of patients with the metastatic disease does not exceed 10-15%. Approximately 50% of melanomas contain point mutation in codon 600 of the BRAF kinase. Specific inhibitors of activated BRAF have demonstrated unprecedented therapeutic efficacy, thus BRAF testing has become a mandatory component of treatment planning for inoperable melanoma. This review discusses key issues, which are related to various clinical, morphological, and molecular genetic aspects of determination of BRAF status in metastatic melanoma.

To analyze the pattern of molecular damages in urinary bladder cancer (UBC), the authors studied allelic imbalance of chromosome loci 9p21 and 17p13 in 22 patients diagnosed as having multiple primary UBC (2 to 5 foci in each patient). The state of markers has no informative value in 3 (13.6%) cases; in 9 (47.4%) of 19 informative cases, deletion of the same allele was determined in at least one of the loci in question in all tumor nodules, which may point to the monoclonal origin of multiple tumors in these patients. Five (26.3%) of the 19 patients exhibited deletion of the same allele in different tumor nodules, which is suggestive of the active process of clonal evolution and the feasibility of tumor subcloning, which does not preclude the possibility of monoclonal origin. Five (26.3%) of the 19 patients had an imbalance of different alleles in varying nodules, which may show the oligoclonal origin of the tumor nodules concerned. The concordant and discordant patterns of molecular damages are encountered virtually with the same frequency in the tumors of multiple primary UBC, which supports the view that its synchronous tumors can develop both monoclonally through intraluminal dissemination of tumor cells and when there are cancerization fields that determine the occurrence of oligoclonal tumors.

It is well known that breast cancers (BC) are divided into 4 molecular genetic subgroups (luminal A, luminal B, HER2/neu-positive, and triple-negative (TNBC). The purpose of the investigation was to comparatively estimate the pattern of expression of Bcl-2, known as a good prognostic marker of BC, in different molecular genetic subgroups and to study the correlation of this protein with proliferative activity index and genetic aberrations on chromosome 17. The investigation covered 290 samples of invasive ductal BC. Bcl-2 expression was identified in 14% of HER2/neu-positive and TNBC cases while 77% of luminal B tumors and 100% of luminal A ones expressed Bcl-2. Loss of Bcl-2 expression correlated with clinically more aggressive BCs having a high proliferative activity and amplification of HER2/neu and chromosome 17 centromere. This may suggest the poor prognosis of luminal B, HER2/neu-positive and TNBC with no Bcl-2 expression and calls for further investigations on larger samples.

By using modified "G2-bleomycin sensitivity assay" above background level of cytogenetic effect considered as a marker of hidden chromosome instability (HCI) has been investigated in 3 groups--liquidators of Chernobyl accident (occupational group 1), patients with lung cancer who denied conscious contact--with ionizing radiation (group of comparison), liquidators with lung cancer (occupational group 2). Significant interindividual variations of cytogenetic effects induced with bleomycin and the lack of positive correlation between background and above background frequencies of chromosome aberrations have been shown in all observed groups. It had been established that occupational group 2 was the most burdened group by expression of the above background cytogenetic effect and, accordingly, number of persons with HCI. The data obtained permit to suggest the existence of the association between radiation-induced increase of individual sensitivity to testing mutagenic exposure and the realization of cancer in persons exposed to ionizing radiation. The results show acceptability of "G2-bleomycin sensitivity assay" under the cytogenetic examination of irradiated contingents for determining HCI as one of informative markers of predisposition to oncopathology.

We investigated association of polymorphisms of interleukin IA (IL-1A), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin-8 (1L-8) genes in elderly patients with predisposition to the development of chronic lym,nphocytic leukemia (CLL). Risk factor of chronic lymphocytic leukemia is a genetic variant -590T IL-4 (OR = 1,45) and protective factor -590S IL-4 (OR = 0,68). Genetic markers -590T IL-4 (OR = 2,46), -590TT IL-4 (OR = 6,65) and mix-590TT genotype of IL-4 allele 703S-IL-5 (OR = 6.70) were associated with stage 0-1 chronic lymphocytic leukemia whereas genetic markers -889T IL-1A (OR = 1,51), -703T IL-5 (OR = 1,52) and a combination of genotype -703ST IL-5 allele-251A IL-8 (OR = 2.85) were related to the development of stage II of the disease. Risk factor for the formation of II-IV stages of chronic lymphocytic leukemia is a genetic variant -703T IL-5 (OR = 1,95).

Ubiquitin-dependent proteasomal degradation is one of the major pathways of non-lysosomal protein degradation in the cell. The ubiquitination process involves several enzymatic reactions and includes the following enzymes: E1--activating, E2--conjugating, and the third--E3--ligating enzymes. E3 ligases determine the specificity of ubiquitination reaction, i. e. what target protein will be subjected to the covalent modification by ubiquitins. The p53b tumor suppressor protein is one of the most intensively studied over the past several decades. Regulation of its activity is a complex and multi-level process that involves many factors. Ubiquitination is one of the major post-translational modifications of p53, and plays a fundamental role in the control of p53 function, its amount, activity and subcellular localization. This review is focused on p53-specific E3 ubiquitin ligases that are potential targets for cancer therapy using small molecule inhibitors.

In the current work we make an attempt to compare cancer cells of one origin, but differing in the expression of CEA protein, a clinical marker of metastatic carcinomas, presumably one of the key factors in metastatic activity. We have explored the morphology of cell colonies in vitro, expression patterns of epithelial markers, the ability of these cells to form tumors and metastases in vivo, and evaluated their stem compartment with the aid of a suicidal genetic construct sensitive to the embryonic stem cell marker, Oct4.

As it was shown by us earlier, side population (SP) cells are more resistant to the low-LET radiation than the other part of mouse melanoma B16 cells (Matchuk et al., 2012). The aim of our research was finding some mechanisms of radioresistance, therefore we analyzed SP and nonSP cell cycle distribution, spontaneous and radiation induced DNA double-strand breaks (number of γH2AX foci) and intracellular NO concentration. The results indicate that SP cells have significantly less DNA double-strand breaks after irradiation at dose of 3 Gy than nonSP cells (24.4 vs 40.3, accordingly, P < 0.05 Mann-Whitney Ucriterion). SP cells are more quiescent compared to nonSP G1/G0 fraction is 85 vs 39%, accordingly, P < 0.01 Mann-Whitney U criterion). Most nonSP cells reside in S, G2/M phases (61%), believed to be rather radiosensitive. Thus, the difference of SP and nonSP cells radiosensitivity can be partly explained by peculiarities of cell cycle distribution. NO concentration is 1.5 times higher in SP than nonSP cells (P < 0.05 Mann-Whitney U criterion); since it is known that NO inhibits apoptosis, being one of the mechanisms of genetic stability maintenance, greater number of spontaneous DNA double-strand breaks in SP cells is unsurprising (P < 0.05 Mann-Whitney U criterion). The above-listed results explain considerably the higher resistance of SP cells to the action of low-LET radiation in comparison with other melanoma B16 cells. Further study of this question can become the basis for development of tools to target SP cells and, ultimately, more effective cancer treatment.

The aim of the review was systematization of the data on discordance in expression of estrogen receptors between primary and metastatic breast cancer, different metastases and repeated analyses of the same tissue. The possible reasons for the phenomenon are discussed. The authors emphasize the need to analyze estrogen receptors in breast cancer metastases, regardless of the receptor status of the primary tumor, for predicting the course of the metastatic disease and providing an adequate treatment of the metastatic tumor in strict accordance with its receptor status during drug therapy. The works cited in the search engine Pub Med to May 2013 were analyzed.

The group (totally 156 postmenopausal women) used for the study of 'standard' (S) and 'associated' (A) genetic markers of potential sensitivity to metformin (MF) consisted of 37 healthy females, 32--with diabetes (DM) without cancer, 64 cancer patients with DM, and 23 cancer patients without DM. No significant difference in carrying of S-polymorphisms was found between DM patients without and with cancer. In cancer patients without DM most characteristic data regarding potential MF-response were detected with polymorphisms of STK11 gene while data on OCT1_rs622342 and OCT1_R61C variants showed opposite trends. In regard of A-markers, the tendency to the more often finding of GC genotype of OLR1_GS01C in DM patients carrying 'MF-positive' variant of OCT1_R61C deserves to be underlined. In patients with new-onset diabetes who carried S-markers of potential response to MF higher insulin resistance (OCT1_R61C and OCT1_rs622342) as well as lower estradiolemia (STK11 and C11orf65) were discovered. Thus, according to genetic S-criteria of sensitivity to MF, DM patients with and without cancer differ in lesser degree than they differ from cancer patients without DM. It can not be excluded, that The efficiency of such criteria might be increased due to combination with A-markers and certain hormonal-metabolic indices.

DNA polymorphism is an important component of the interindividual variation in reactions of patients to the same drugs. In this work, evaluation of the association between polymorphisms in 106 genes involved in key processes of cellular activity (xenobiotic metabolism, DNA repair, the cell cycle, and apoptosis), and outcomes in a cohort of Yakut ovarian cancer patients receiving cisplatin-based chemotherapy was carried out. The polymorphism in the CDKN1B gene (rs34330) was found to be associated with complete tumor response and progression-free survival. SNPs in EPXH1 gene (rs2234922 and rs2260863) were correlated with hearing impairment. A SNP in NBN gene (rs1063045) was associated with severe emesis.

The results of the examination of association of polymorphisms of DNA repair genes and chromosomal aberrations in lung cancer patients are discussed. A significant positive association between the hOGG1 G/G genotypes, XPD G/G genotype and lung cancer was found. The hOGG1 C/C genotypes were significantly negatively associated with lung cancer. The patient chromosomal aberration frequencies were significantly higher than in control. Carriers of all APE1 and XPD genotypes, XRCC1 G/G genotype, ADPRT T/T genotype, hOGG1 C/C and Ser/Cys genotypes had statistically significant differences in the level of the chromosomal aberrations between patient and control groups. Statistically significant differences in the level of chromosomal aberrations between XPD T/T and G/G genotype of lung cancer patients were observed.

Currently, gerontologists, evaluating the effectiveness of various impacts on the aging process, as a rule, use a variety of molecular cell biomarkers of aging. This provides much more rapid results than in the case of the survival curve obtaining. However, in many cases the usefulness of these biomarkers of aging is grounded in works devoted to what is called cellular/cell senescence. Unfortunately, the evolution of the term in recent years has led to the loss, to a large extent, of its original meaning, that is the changes of the cells during their replicative senescence ("on Hayflick's grounds"), similar to the changes of cells in the aging organism. At present, most of the work in this area is related to the induction of the relevant changes in the cells (usually transformed) by various DNA damaging factors. Such an approach, although is very important to define a strategy to fight cancer, but, yet again, takes us away from the study of the real mechanisms of organismal aging. In addition, there are reasons to believe that the biomarkers of aging, proposed by these studies (and in particular, the most popular of them--the activity of senescence-associated beta-galactosidase), are related, as a rule, to the proliferative status of the cells, which in the whole body is generally determined by proper implementing the program of development and differentiation, leading to the emergence of tissues and organs composed of postmitotic or very slowly proliferating cells. Therefore, the possible disabling the aging program, apparently, will not lead to any changes in the age dynamics of those biomarkers of aging. This conclusion brings us back to the need for obtaining the survival curves of experimental animals or humans as the only true (although the most time- and money-consuming) approach to evaluating the effectiveness of the modification of the aging process.

The article discusses results of the structural and functional analysis of molecular genetic abnormalities in various malignant tumors. Investigations have discovered more than 20 new markers for sporadic breast cancer. Several of them formed the test system, allowing the diagnosis with a specificity of 100%. Appearance of TMPRSS2/ERG4 chimeric gene is a frequent tumor-specific event, its expression is correlated with more aggressive forms of prostate cancer, may serve as a molecular marker for tumor cells and androgen assessment of tumor response to hormonal therapy. The effective systems for the early diagnosis of cervix and endometrium cancer were developed as well. Mutations in the VHL, deletions of chromosome 3 and methylation of several genes can predict the course and selection of effective therapy of clear cell kidney cancer, a number of molecular markers were identified for early diagnosis and prognosis of recurrence of bladder cancer. For diagnosis, prognosis and treatment of brain tumors we developed an effective complex system of markers. Protocol of molecular genetics investigation reveals the cause of the disease by more than 90% of patients with retinoblastoma. In order to study abnormal methylation in tumor genomes an innovative technology AFLOAT has been developed that allows to efficiently identify new markers with diagnostic value. Test systems of molecular genetic and epigenetic markers for early diagnosis and prognosis as well as for cancer therapy optimization have shown to be effective, have been approved for use in clinical practice and are being introduced into practical healthcare.

KRAS mutations in patients with metastatic colorectal cancer (CRC) are a negative marker of the effectiveness of anti-EGFR therapy and have prognostic significance. KRAS genotyping was performed in the material from patients with metastatic CRC. KRAS mutations were determined in tumor DNA from archival biopsies of 573 patients using PCR and sequencing. Mutations in the exon 2 of the KRAS gene were detected in 36.3% of cases of CRC, while often in women (41.1%) than in men (31.2%). There were identified eight types of KRAS mutations, the most frequent--replacement of G12D (33.7%), G12V (32.7%) and G13D (12.5%). There were revealed differences in the frequency and spectrum of KRAS mutations in CRC of various locations; in tumors of the rectum dominated mutation G12V (39%). The Russian CRC patients find out a higher frequency of mutations G12V and a lower frequency of mutations G13D, than patients from Europe and it should be taken into account when assessing the response of CRC patients with different mutant KRAS status on chemotherapy and targeted therapy.

Clinical and genetic analysis of 24 Russian patients with attenuated form of family colon adenomatosis was undertaken. On the basis of obtained clinical and genetic data it was defined the algorithm of therapeutic measures in this group of patients--from dynamic monitoring or endoscopic polypectomy to performing extensive resections of the colon in situations associated with cancer development, an increase of the intensity of growth of polyps or an appearance of villous lesions. Some of the patients had molecular-genetics causes of a weakened form of family adenomatosis.

In present publication we describe for the first time the obtainment of cancer stem cells from a weakly metastatic human colorectal carcinoma cell line MIP101 via selecting from the native population the cells that express intensively an embryonic stem cell marker, POU5F1 (Oct4). We provide the evidence that these cells possess an elevated clonogenic and tumorigenic potential when compared to the native population, and this correlates to the hypothesis of cancer stem cells' primary role in the development of malignant neoplasms.