There were analyzed associating of functional polymorphism of the promoter regions of genes MMP2 C--1306T, MMP 9 C--1562 T, MMP3 5A--1171 6A in a group of healthy women and breast cancer patients in order to identify informative markers associated with the risk of developing the disease. The study included 395 DNA samples from women with breast cancer and 329 healthy women. Genotyping of polymorphisms was carried out by restriction analysis of amplification products (RFLP-analysis). Among female patients there was revealed significantly seldom a carrier of 6A6A MMP3-1117 and MMP 9-1562TT genotypes and also significantly increased the frequency of MMP3 5A6A genotype. The risk of lymph node metastasis reduced in patients with MMP9-1562CC genotype. Conversely heterozygosis at this position could be regarded as risk factor for metastasis. It was revealed associating of MMP3 5A6A genotype with the degree of malignancy.

Karyotypes of 9 malignant melanoma patients has been described. It is ascertained that most often the damage is observed in chromosomes 1, 6, 7, 9 and 17, which is consistent with the data in the literature. Besides chromosomes 5 and 13 are also often involved in different rearrangements. Recurring aberrations are not discovered. Any correlation between survival and non-recurrent chromosomal aberrations is not discovered.

The study was designed to analyse the relationship between EGFR mutation and clinico-pathological features of lung adenocarcinoma in residents of southern Russia taking account oftheir age and sex, localization of the primary tumour, its cell differentiation, regional metastases, stage of disease and smoking status of the patients with mutant and wild-type EGFR genes. The frequency analysis included 29 somatic mutations in EGFR exones 18-21. The study revealed statistically significant associations of EGFR gene mutations with gender, smoking and stage of disease.

Considerable progress has recently been achieved in understanding molecular medicine in general and vell molecular biology in particular. Molecular medicine is a scientific discipline studying man under normal condition and pathological changes at the cellular-molecular level with reference to gene activity and function of protein mediators responsible for delivery of information to various organs or systems of the body and cell-to-cell interaction.

Melanoma holds a leading position in the mortality from skin tumors. Standard treatment of metastatic melanoma allows tumor remission to be achieved only in a small subset of patients. Studies on melanoma molecular pathogenesis led to the identification of several causative genetic events and, consequently, to the development of novel targeted drugs. More than a half of melanomas contain amine acid substitutions in serine-threonine kinase BRAF. Clinical trials involving specific BRAF inhibitors--vemurafenib and dabrafenib--demonstrated high efficacy of these agents towards BRAF-mutated melanoma. MEK inhibitors may show activity against both BRAF--and NRAS-driven tumors. Mucosal and acral melanomas frequently contain mutation in KIT receptor and can be successfully treated by imatinib. There are novel therapeutic monoclonal antibodies targeted against immunosuppressive molecules CTLA4, PD-1 and PD-L1. In some instances these drugs allow to obtain exceptionally prolonged responses. Whole genome sequencing led to the identification of new melanoma genes, e.g. GRIN2A, TRRAP, PREX2, RAC1, STK19, PPP6C, etc. Molecular testing, especially BRAF mutation analysis, has become a mandatory part of melanoma diagnosis. Nevertheless, despite the revolution in melanoma treatment, the prevention of excessive ultraviolet exposure, cancer awareness and early diagnosis remain the main tools for the management of this disease.

The paper describes 6 cases of atypical teratoid/rhabdoid tumors (ATRT) in the complete absence of classical rhabdoid elements isolated from 25 INI1-negative central nervous system tumors investigated in the period 2006 to the present time. Analysis of the specific features of the histological structure of INI1-negative tumors could identify a few histological types of ATRT according to the conventionally standardized criteria for diagnostic search.

The effect of E-cadherin on the prognosis of Stage I-II non-small cell lung cancer (NSCLC) was investigated. Tumor E-cadherin expression and its correlation with the clinical and morphological characteristics of a patient, as well as the prognostic role of this marker were studied. It was ascertained that the E-cadherin expression did not depend on patient gender and age, tumor histological pattern, location, grade, and pT category, but it was significantly related to the pN1 category (p < 0.0001). Univariate analysis revealed that the histological pattern of a tumor, nodal status, resection type (lobectomy/pulmonectomy), and E-cadherin expression level were significantly correlated with patient survival. Multivariate analysis showed that the important predictors were tumor histological pattern and resection type (p = 0.01 and p = 0.00004, respectively). A more complete study of the prognostic and predictive role of E-cadherin expression in patients with Stage I-II NSCLC will help identify a prognostically unfavorable group of patients who may be given additional treatment in the postoperative period.

The technique to detect all possible variants of mutations in 12, 13 and 15 codons of gene KRAS was developed on the basis of the pyrosequencing technology. The analytical characteristics of the developed technique were identified. The limit of detection for mutations G34T, G35A and G38A detected on the cloned control samples consisted 3%. The limit of blank for various mutations consisted from 0.3% to 4.1%. The system was tested on clinical samples. The 7 different types of mutations were identified and detected in quantitative format. No discrepancy of pyrosequencing data with results of sequencing according Sanger was established.

The DNA of virus of human papilloma of high carcinogenic risk was detected in 116 cervical samples. At that, the morphological symptoms of background processes are detected in 19 samples, CIN 1 in 9, CIN 2 in 23, CIN 3 in 54 (and out of them carcinoma in situ in 13), epidermoid cancer (squamous cell carcinoma) in 11 cases. The viral load of human papilloma of high carcinogenic risk in all samples of DNA exceeded threshold of clinical value (3 lg copies of DNA of human papilloma/105 cells). The genetic typing of human papilloma of high carcinogenic risk revealed the dominance of human papilloma of type 16 in 49.7%, type 33 in 15.3%, type 31 in 12.3% and type 45 in 5.5%. In women with background processes in cervix of the uterus DNA of human papilloma type 16 was detected more often in episome form. In case of dysplastic alterations of epithelium and cervical cancer DNA of human papilloma type 16 is detected in mixt form with different degree of integration into cell genome.

Prognostic significance of p53 expression in tumoral cells was studied in patients, suffering mammary gland cancer (MGC). The higher p53 mutative type expression in the tumor, the more aggressive is MGC development, the indices of general and disease-free survival are poorer, so prognosis is poorer as well.

MYCN gene amplification and 1p deletion in neuroblastoma patients are associated with poor prognosis and commonly used for patient's stratification into risk groups. MYCN copy number and 1p deletion status were analyzed with multiplex ligase-dependent probe amplification (MLPA), PCR and FISH. MYCN amplification was revealed in 21 patients (17.2%) simultaneously by MLPA and PCR. In 28 cases (23.0%) 2p gain was detected. 1p deletion was revealed in 28 patients (23.0%) while concordance between PCR and MLPA achieved 95.8%, PCR and FISH - 90.9%. Mean follow-up time achieved 42 months (ranged from 1 month to 13 years). Event-free survival and overall survival in MYCN-amplified patients as well as in patients with 1p deletion were significantly lower comparing with MYCN-negative patients or patients without 1p deletion.

About 3% of cases of gastric cancer (GC) cases are due to hereditary predisposition. Molecular causes of inherited predisposition to diffuse GC among Russian patients have not been studied. In the present work there was performed the molecular genetics study in 9 probands with signet-ring cell GC. Search of hereditary mutations was conducted in a suppressor gene of diffuse GC - the gene CDH1. We have discovered a new hereditary mutation (c.1005delA) and one rare variant (s.2253C> T). Frequency of hereditary mutations in sample of patients Russian was 1/9 (11,1%).

In preparation of the therapeutic genetic constructs aimed to the gene-programmed enzymatic transformation of the non-toxic prodrug into toxin within cancer cells the right choice of regulatory elements (promoters and enhancers) is essential. This is widely accepted that the efficiency of the gene therapy constructions is dependent, in particular, on the strength of promoters driving the expression of the therapeutic genes. In this work we demonstrated, using the melanoma-specific promoters and enhancers of human melanoma inhibitory activity and mouse tyrosinase gene, that for the development of cytotoxic effect the promoter strength is not of primary importance. In the case of HSVtk, coding for the herpes simplex virus thymidine kinase, and FCU1, coding for cytosine deaminase/uracil phosphoribosyltransferase hybrid protein genes, their cytotoxic activity was determined by the quantity of the added prodrug.

We have examined for the first time the relationship between the expression of PAPP-A metalloproteinase and insulin-like growth factors (IGF-I, IGF-II, VEGF) and transcription factors (NF-kappaB, HIF-1) playing an important role in pathogenesis of cancer. We also demonstrated a positive association between the level of PAPP-A metalloproteinase and the level of growth (VEGF and IGF-I) and transcription factors (NF-kappaB p50, NF-kappaB p65, HIF-1alpha). The current findings suggest an important role of PAPP-A in regulation of bioavailability of IGF-I, VEGF, activated forms of NF-kappaB, and alpha-subunits of HIF-1 in endometrial tumors.

To determine the significance of the angiogenic activity estimated from the gene expression of the vascular endothelial growth factors (VEGFs) VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR1, VEGFRls, VEGFR2, and VEGFR3 in the mononuclear cell fraction of bone marrow (BM) aspirates with tumor plasma cells predominating in different variants of the course of multiple myeloma (MM).

To evaluate the efficiency of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloblastic leukemia in first remission depending on the regimens of conditioning, the source of a graft, and the characteristics of a donor and a recipient.

Malignant brain tumors are noteworthy for a lot of genetic disorders that show itself as decreased or increased gene function of different genes and lead to tumor development. The differences in the molecular genetic profile can identify several subtypes of malignant gliomas, which are distinguished by both their clinical course and susceptibility to drugs. This can be the basis for developing individualized therapy options in patients with malignant gliomas.

Non-small cell lung cancer (NSCLC) comprises 80% of all lung cancers and is characterized by multiple genetic alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI). The aim of the study was to analyze of molecular-genetic alterations in tumor and tissue surrounding the tumor to determine genetic features of different histological types of NSCLC and its possible associations with clinicopathological parameters of patients. A microsatellite analysis of chromosomal regions 12p23.3, 2q35, 3p14.2, 3p22.2, 3p26.3, 9p22.1, 17p13.3 was performed. The frequency of genetic alterations in NSCLC was 50% in average. LOH/MSI in the tumor surrounding tissue at 2 and 5 cm. from tumor was not detected. There were statistically significant associations between LOH and/or MSI and the tumor stage, its histological type and smoking status. The found genetic alterations can be used as molecular markers of squamous cell lung cancer in difficult diagnostic cases and appraised as prognostic markers.