Almost 80% of cases of hereditary retinoblastoma do not have a family history and arise as a result of de novo mutations in the RB1 gene. An NGS test was performed on 208 unrelated patients with sporadic RB, including 145 patients with a unilateral form and 63 patients with a bilateral one. In the group of patients with bilateral RB, pathogenic variants in the RB1 gene were detected in 90.5% (57/63) cases. In 4.8% (3/63) of patients, a mosaic variants were determined. In the group of patients with unilateral RB, changes in the RB1 gene were detected in 17.9% (26/145) cases. Among the examined patients, somatic mosaicism was detected in 9.0% (13/165) cases. NGS allows us to determine the allelic frequency of variants, which makes the search for somatic mosaicism effective.

A comprehensive molecular genetic examination of patients with diagnosis of tuberous sclerosis was carried out. The complex includes NGS with deep sequencing for detecting point mutations and indels, MLPA for identification of extended deletions, and Sanger sequencing. Mutations was found in 96,5% cases from 202 samples. Point mutation and indels were found in 93,3% cases, extended deletions were found in 6,7%. Mutations with low allelic representation were found in 5,9%.

The study was conducted of DNA from peripheral blood of 1000 patients with clinical signs of neurofibromatosis type 1 or neurofibromatosis type 2. The genetic testing included massive parallel sequencing, multiplex ligation-dependent probe amplification, Sanger sequencing. The pathogenic mutation was identified in 70.2% of the cases, affecting NF1 and NF2 genes in 672 and 30 cases, respectively.

Breast cancer (BC) is a complex, genetically heterogeneous disease. The results of numerous studies have proven the important role of miRNA in tumor progression. miRNA sequences are highly conserved. Any variants in these sequences as well as the binding sites of miRNA in the target genes are supposed to be under negative selective pressure. miRNA that alter the expression of genes have been identified to play a significant role in BC regulation. The present study is aimed at investigating the involvement of SNPs in miRNA-binding sites as risk factors for the development of BC. A case - control study was performed to evaluate genetic variants of BRCA1, BRCA2, BRIP1, RAD51, RAD52, MRE11A, NBN, ERBB4, PTEN genes as BC risk factors. The results of the present study suggest that genetic variants rs11895168 / ERBB4 and rs7180135 / RAD51 are associated with breast cancer risk.

The most serious complication of breast cancer (BC) is metastasis, which causes more than 80% of all deaths from BC. The process of lymph nodes metastasis is not well understood. 47 paired frozen breast tissue samples were collected. All patients have no radiation therapy and chemotherapy. We studied the expression of two genes - FN1 and PDGFRβ - for the investigation of their relationship to lymph nodes metastasis. Expression of the FN1 and PDGFRβ genes showed an association with the risk of early metastasis (p = 0.012 and 0.03, correspondently). The relative risk (RR) for FN1 was RR = 1.5, 95% CI 1,1-1,9, and for PDGFRβ RR = 2.4, 95% CI 1,1-5,2.

Within a genome-wide study, we have identified abnormal methylation of the dihydropyrimidinase DPYS gene promoter in breast cancer (BC). Since dihydropyrimidinase is involved in the catabolism of pyrimidine antagonists, the role of DPYS methylation in determining the sensitivity of tumors to such drugs is of interest. Detailed analysis of DPYS methylation in 29 biopsy samples of the LumB BC subtype obtained before neoadjuvant chemotherapy (NACT) with pyrimidine antagonists discovered that tumors with methylated DPYS promoter are more sensitive to NACT than tumors with unmethylated DPYS (AUC=0.87). Our results indicate the advisability of including pyrimidine antagonists in the LumB BC NACT regimens for patients whose tumor biopsy samples taken before treatment demonstrate hypermethylation of the DPYS promoter.

Based on the results of genome-wide screening of differential methylation in breast cancer samples (BC), we have identified abnormal demethylation of the LTB4R leukotriene receptor gene CpG island, which can lead to its ectopic expression. In this paper, we used the data obtained for 1083 BC samples under the TCGA-BRCA project to determine impact of LTB4R expression on the effectiveness of treatment with cyclophosphamide. Analysis of survival curves for patients with triple-negative (TN) breast cancer and high expression of LTB4R showed an increase in overall survival of patients treated with cyclophosphamide (p <0.05). For LumB BC subtype, the effect of cyclophosphamide was not dependent on LTB4R expression. The results obtained expand the possibilities of personalizing BC therapy.

Breast cancer (BC) occupies a leading position among neoplasms in women in terms of morbidity and mortality. Despite the advantages of neoadjuvant chemotherapy (NACT) which allows achieving high treatment results, a significant part of patients with residual tumor and significantly worse prognosis remains. We have carried out a genome-wide DNA methylation analysis and identified 33 genes methylation of which distinguishes breast tumors with different responses to NACT. Our findings provide the basis for development of test systems for diagnostics of potential sensitivity of breast tumors to NACT via DNA methylation analysis.

Our previous studies have shown that BRCA1 gene deficiency caused by changes in the tumor such as low expression, deletion, loss of heterozygosity, etc., can be associated with the effectiveness of chemotherapy and the disease prognosis. However, even in the absence of these factors, the effectiveness of taxotere therapy was variable. This may be due to the availability of another BRCA1 gene somatic changes in the tumor tissue and their determination will help to define the personalize treatment strategy for each breast cancer patient. Here we investigated the entire spectrum germline and somatic mutation of coding region of the BRCA1/2 gene in tumor tissue. Overall, our results suggest that it makes sense to take into account not only identified germline mutations, but also somatic changes in the BRCA1/2 gene when appointment taxotere

To understand mechanisms of interaction between extracellular matrix proteins and transmembrane receptors, as well as their role in maintaining the structure and function of breast tissue in norm and in cancer, an important issue is to determine the contribution of changes in the expression of these proteins to the processes of development, growth, invasion and metastasis of breast cancer. Studies of the methylation status of genes encoding laminins, nidogens, integrins, cadherins, matrix metalloproteinases and their inhibitors in normal and tumor tissues are necessary to determine the roles of these genes and the mechanisms of their regulation in cancer. We have studied methylation status of these genes in normal and tumor tissues of the mammary gland in order to search for epigenetic markers associated with the clinical and morphological characteristics of the tumors.

Progress in genetics and molecular research enabled discovery of mutations in BRCA1 and BRCA2, leading to the development of hereditary breast (BC) and ovarian (OC) cancer. Genetic testing contributes to early diagnosis and targeted prevention of these cancers. Objective: To investigate the prevalence of pathogenic variants in BRCA1 and BRCA2 genes in patients with BC/OC and in a population-based sample without oncological diseases. Methods: 156 patients with diagnosed BC/OC were included in the study consecutively. In addition to it, 359 women from a population-based sample ESSE-Vologda were recruited in the study. Variants of BRCA1 and BRCA2 were detected using a custom panel. Results: Among cancer patients there were 5 carriers (3.21%) of mutations in BRCA1 (4 - rs80357906, 2.56%; 1 - rs80357711, 0.64%) and 1 carrier (0.64%) of rs80359550 in BRCA2. In a population-based sample no mutations were identified. The presence of BRCA1 (rs80357906, rs80357711) or BRCA2 (rs80359550) variants increases the risk of BC/OC at least 2.63 times (р=0.0009). Conclusion: Detection of pathogenic variants in BRCA1 and BRCA2 could facilitate early diagnosis and timely prevention of BC and OC.

The aim of the work was to assess the relationship of chromosomal aberrations of the BRCA1, NF-κB1, PARP1 genes in breast tumor tissue with the effect of chemotherapy and prognosis of the disease. The study included 85 patients with luminal stage IIA-IIIB breast cancer, with a morphologically verified diagnosis, aged 25-68 years (47.8±1.1). As a result of the study, the CNA frequency of the studied genes was estimated. It was found that the highest deletion rate is observed in the BRCA1 gene (36%, 30 cases out of 85). The frequency of amplification of PARP1 in the studied group of breast cancer patients reaches 62% (53 cases out of 85). The smallest number of chromosomal aberrations is observed in the NF-κB1 gene; in only 22 patients, deletions and amplifications of this gene are observed (26%). it was found that the deletion of the BRCA1 gene is associated with a good response to neoadjuvant chemotherapy, regardless of the presence of chromosomal aberrations of other genes. Moreover, amplification of PARP1 is associated with a poor prognosis of the disease.

The aim of this work was to study changes in the breast tumor transcriptome and the amplification status of the long arm of chromosome 8 (with locus 8q24) and in the process of pre-surgery chemotherapy. The study used paired samples of biopsy material before treatment and surgical material from 60 patients with breast cancer of luminal B subtype who received 4-8 courses of NAC. It was shown that in 65% of cases, amplification of 8q is preserved in the tumor after NAC. Top-10 DEG signaling pathways in the tumor of breast cancer patients before treatment and after NAC with the presence of amplification of 8q are shown. DEG of patients with different amplification statuses of 8q (with region 8q24) before treatment and after NAC overlap in8 genes. In the residual tumor of patients with amplification of 8q, an increase in the expression of stemness genes GSK3B, MYC, GATA3, SMAD4, SMAD2 participating in WNT and TGFb syngnaling was found. The study shows a large effect of amplification of the long arm of chromosome 8 on the tumor transcriptome in breast cancer, regardless of other molecular genetic features. Amplification of 8q involving region 8q24 leads to a significant shift in the level of transcription of a large number of genes precisely after exposure to chemotherapy.

To test the hypothesis about an association between ABCC11 538G>A polymorphism and breast cancer we analysed the frequency of this functional SNP in case-control breast cancer study of Caucasian women from Russia (one of top-ten mortality rate countries) but found no evidence for increased breast cancer risk.

Two critical polymorphisms of the ATM gene, (rs664143 (A> G) and rs189037 (G> A), were studied in a sample of 214 patients with breast cancer and ovarian cancer and 389 women in the control group (≤45 years old) belonging to the Chechen population. An analysis of the conjugation of allelic variants of the ATM gene with a risk of developing breast and ovarian cancer showed an increased risk of developing ovarian cancer in case of carriage of the G allele polymorphism rs189037, but no reliable associations were found with breast cancer).

The nature of the effect on the formation of breast cancer and the reproductive system in 409 women with breast cancer and 60 with cancer in the Chechen population of four functionally significant polymorphisms of the LIG1 and LIG3 genes (rs156641, rs20579, rs1052536, rs4796030) was studied. Genotyping was performed using PCR analysis. We identified the candidate genotypes that influence the risk of developing breast and ovarian cancer.

The authors analyzed available data in modern literature on the role of genetic testing for mutations in genes responsible for predisposing to hereditary cancers of reproductive organs in women. They are looking at data on the importance of using genetic testing in clinical practice to predict the disease development, need for follow-up monitoring in the presence of mutation load, and determination of combined chemotherapy policy for malignant neoplasms.

Ovarian cancer (OV) is an important public health problem worldwide. This oncopathology has the highest mortality rates and the lowest survival rates during the first year among malignant tumors of the female reproductive system. In this regard, the development and improvement of methods for the early diagnosis of cancer is one of the priority tasks of gynecological oncology. This paper presents a search for associations of a variant of the splicing site c.1047-2A> G in the CDK12 gene with the development of ovarian cancer in the Republic of Bashkortostan.

Ovarian cancer (OC) is one of the most common malignant neoplasms of the organs of the reproductive system. In this paper, we analyze the associations of polymorphisms rs757210 в of the HNF1B gene with the risk of developing OC in women from the Republic of Bashkortostan.

29,084 Ufa residents were examined for cervical cancer using HPV technology Digene-test (Digene-test, QIAGEN), as part of a pilot project of organized combined screening, followed by cytological examination of HPV positive women. Women were 30-39 years old. Positive results were detected in 2991 cases, which is 9.8% of all examined women. Precancerous changes in the cervix was revealed in 274 patients, and carcinomas - in 19 patients.

A total of 584 patients with uterine fibroids and 391 healthy controls were recruited for the study. Genotyping of single nucleotide polymorphisms (SNPs) of the HIF1A and HIF1B genes (rs2301106, rs2301113, rs1951695, rs2057482, rs4899056 HIF1A and rs3738493, rs10847 HIF1B) was performed using real-time PCR). The protective effect of rs10847 HIF1B against the risk of uterine fibroids was revealed (OR=0.78, 95%CI=0.63-0.95; P=0.016). The molecular mechanisms of the involvement of rs10847 HIF1B to the pathogenesis of uterine fibroids are discussed.

A total of 552 females with uterine fibroids and 337 age-matched healthy controls were recruited for the study. Genotyping of single nucleotide polymorphisms (SNPs) of rs713041 GPX4, rs4902346 GPX2, rs41303970 GCLM, rs17883901 GCLC, rs1050450 GPX1, rs1799811 and rs1695 GSTP1, rs2551715 GSR, rs1801310 GSS, rs4820599 GGT1, rs7674870 SLC7A11 were done using Taq-Man-based assays. Genotyping of +/0 GSTM1 and +/0 GSTT1 polymorphisms were done using multiplex PCR. Polymorphism rs7674870 SLC7A11 was associated with increased risk of uterine fibroids (OR=1.25, 95%CI=1.03-1.50; p=0.02); rs2551715 GSR was associated with decreased risk of disease (OR=0.83, 95% CI=0.70-0.99; p=0.04)

A total of 603 females with uterine fibroids and 398 healthy individuals from Central Russia were recruited for the study. Genotyping of single nucleotide polymorphisms (SNPs) of the aryl hydrocarbon receptor signaling pathway genes (rs2066853 AHR, rs2292596 AHRR, rs2228099 ARNT, rs1048943 CYP1A1, rs762551 CYP1A2, rs1056836 CYP1B1, rs1800566 NQO1) were done using Taq-Man-based assays. Polymorphisms rs2228099 ARNT (OR=1,58; 95%CI=1,19-2,09) and rs1048943 CYP1A1 (OR=0,59; 95%CI=0,40-0,91) were associated with predisposition to uterine fibroids.

Adenomatous polyposis syndromes are severe hereditary diseases, characterized by the development of tens and hundreds colonic polyps and an extremely high risk of colorectal cancer without timely surgical treatment. Two hundred and forty Russian patients with more than 20 adenomatous colonic polyps were included in genetic study. Hereditary heterozygous mutations in the APC gene were detected in 157 patients, and biallelic mutations in the MutYH gene - in 14 patients. According to our results, patients with more than 100 polyps should undergo colectomy before 25 y.o.

A total of 256 patients with colorectal cancer (134 males, 122 females) and 608 age- and sex-matched healthy controls (279 males, 329 females) were recruited for the study. Genotyping of single nucleotide polymorphisms (SNPs) I462V (rs1048943) CYP1A1, -154A>C (rs762551) CYP1A2 and L432V (rs1056836) CYP1B1 were done using Taq-Man-based assays. Polymorphism rs1056836 (substitution L432V) CYP1B1 was associated with increased risk of colorectal cancer in the population from Central Russia: OR=1,48, 95%CI=1,07-2,04; p=0,02.

Study objective is to assess the prevalence of rare mutations in the EGFR, KRAS, NRAS, BRAF genes, as well as the proportion of the mutant allele frequency (AF) in the samples of patients with lung cancer and colorectal cancer. Materials and Methods: 199 samples of DNA isolated from paraffin blocks was studied using next generation sequencing. Study Results: rare mutations in colorectal cancer were detected in 12.8% of patients. 20% of the samples had AF <15%. Rare mutations in lung cancer were observed in 24.2%. 27% of the samples had AF <15%. Conclusion: Next Generation Sequencing (NGS) may be recommended as a routine method for detecting somatic mutations in a tumor. NGS has great diagnostic capabilities compared to PCR or Sanger sequencing.

The introduction of new drugs based on the inhibition of immune control points (ICР) into cancer therapy has significantly improved the prognosis for patients. However, such therapy is not always effective. To reveal the possible reasons for this, we studied the expression levels of PD-L1 and other ICР genes - IDO1, CEACAM1, PVR, TDO2, CD276, GAL9 and ADAM17 in samples of clear cell renal cell carcinoma. The analysis revealed the genes most often expressed together with PD-L1 - IDO1, TDO2, CD276, GAL9 and ADAM17. Significant correlation with the expression of PD-L1 was found for the expression of ADAM17, PVR, and CD276 genes. The data obtained may be important for the further development of therapy based on blocking ICP, including PD-L1.

Renal cell carcinoma (RCC) is a common renal neoplasia of various morphological types, among which clear cell RCC is most common. It is believed that the miRNA-29 family, including miRNA-29a, miRNA-29b and miRNA-29c, is associated with aggressiveness and prognosis of malignant neoplasms and can be a promising biomarker for predicting the initiation, progression and pathogenesis of cancer. Expression levels of miRNA-29a, -29b, and -29c were determined in 30 pairs of normal and tumor tissue samples from the kidneys of patients with RCC using real-time quantitative PCR. A statistically significant decrease in miRNA-29a expression was found (Fold change = 0.213; p-value = 0.0016) in tumor tissue compared with normal renal parenchyma.

Сurrently available prognostic classifications cannot clearly identify the cases of low and high risk of bladder cancer (BC) progression. We have analyzed the FGFR3, PIK3CA, TERT, and TP53 mutations in 101 BC patients. The correlation of TP53 mutations and absence of mutations in FGFR3, PIK3CA and/or TERT with tumor grade was observed; up to 25% of non-muscle invasive BC cases in low and intermediate risk groups harbor the mutations associated with the disease progression.

The analysis of the frequency distribution of alleles/genotypes of polymorphic loci rs1799750 and rs494379 of the MMP1 gene, rs2285053 of the MMP2 gene, rs3025058 of the MMP3 gene, rs3918242 and rs17576 of the MMP9 gene, rs2276109 of the MMP12 gene, rs8179090 of the TIMP2 gene and rs9619311 of the TIMP3 gene in 314 patients with gastric cancer, as well as in 339 healthy individuals from the Republic of Bashkortostan. Using the APSampler algorithm were identified combinations of alleles/genotypes associated with increased and reduced risk of developing the disease.

The analysis of IL-17A G197A and IL-17FA7488G in 150 patients with gastric cancer and 103 healthy. The studied groups are comparable by gender and age. Among the controls, the genotype distribution for each SNP is in Hardy-Weinberg equilibrium. (p> 0.05). The frequencies of IL-17F A7488G genotypes in cases (GG - 38.7%; GA - 39.3% and AA, 22%) significantly differed from those in the control (GG, 16.5%; GA, 60.2% and AA, 23.3%). The genotypes of IL-17A197 in cases also differed from those in the control (AA 40.7%; AG, 48.7%; GG, 10.6% and AA 17.5%; AG, 70.8%; GG, 11.7%, respectively). Our data may indicate that the genotypes GG, IL-17F A7488G and AA, IL-17A197 are associated with a risk of developing gastric cancer.

Epigenetic mechanisms regulate chromatin structure and create stable patterns of gene expression during cell life. Violation of epigenetic regulation plays a significant role in carcinogenesis, invasion, recurrence and metastasis of tumors, and can serve as a useful clinical marker. Mutational profiling of epigenetic regulation genes in tumor samples of gastric cancer will allow us to identify new clinical and prognostic markers and additional targets for the treatment of patients with gastric cancer. This article presents the first results of a study of somatic mutations in the epigenetic regulation genes carried out using NGS.

The expression levels of miR-146a and the target gene of this miRNA, NF-kB, in gastric cancer (GC) samples at different stages of metastasis development were studied. The expression of miR-146a in the samples of the GC decreased with the involvement of regional lymph nodes in the metastatic process. A negative correlation was found between the expression level of miR-146a and the number of regional lymph nodes damage (Spearman’s correlation coefficient (R) was R = - 0.61; p 0.005). On the contrary, NF-κB gene expression increased with lymph node metastases. An inverse correlation was found between miR-146a and NF-κB (R = -0.76; p 0.03). The first detected negative correlation of expression between miR-146a and NF-κB may indicate activation of the NF-κB signaling pathway in GC cells with a decrease in miR-146a expression. Apparently, this signaling pathway is important in the development of metastases of gastric cancer.

In the presented “case-control” study 670 residents of the Kemerovo Region subject to age, sex, ethnicity and smoking status were included. We formed two groups: 1) “Case” - 304 newly diagnosed lung adenocarcinoma patients undergoing a medical treatment in the Kemerovo Regional Oncology Center; 2) “Control” - 366 healthy donors of the Kemerovo Regional Center of Blood Transfusion. Statistical analysis were performed using SNPstats (http://bioinfo.iconcologia.net/SNPstats), «Statistica 10.0» (StatSoft, Inc., USA). A significant association obtained between the CYP1A1 (rs4646903Т>С), GSTТ1(del) and lung adenocarcinoma.

The present study examined the possible relationship between human papillomavirus (HPV) and the occurrence of lung cancer (RL). Currently, the effect of viral infection on the course of this malignant neoplasm has not been established for certain. In addition, there is no work on the Russian population on comparing the survival of virus-positive and virus-negative patients with a diagnosis of RL.

Small cell lung cancer (SCLC) accounts for about 15-20% of all lung cancer cases and is one of the most malignant tumors. In more than 90% of cases of SCLC, mutations of the TP53 gene are detected. The aim of our study was to analyze the structural changes in the 17p13 chromosomal region in patients with SCLC from the Republic of Bashkortostan. We used 70 lung tissue samples from patients with SCLC. The study was conducted using MLPA. Deletions and/or duplications in the coding regions of the TP53 gene were detected in 40% of the samples, including duplications of the first exon (23% of the samples) and deletions of the 4-6th and 11th exons of the TP53 gene (17% of the samples). Besides, the CHEK2 c.1100delC mutation was detected in four samples.

In the presented «case-control» study 540 residents of the Kemerovo Region subject to age, sex and smoking status were included. We formed two groups: 1) «Case» - 270 newly diagnosed lung cancer patients undergoing a medical treatment in the Kemerovo Regional Oncology Center; 2) «Control» - 268 healthy donors of the Kemerovo Regional Center of Blood Transfusion. Statistical analysis were performed using SNPstats (http://bioinfo.iconcologia.net/SNPstats), «Statistica 10.0» (StatSoft, Inc., USA). A significant association obtained between the APEX1 (rs1130409), hOGG1 (rs1052133), XRCC1 (rs25489), АТМ (rs18015), XPC (rs2228001)) and lung cancer.

Chronic myeloid leukemia (CML) is an oncohematological disease. Great success has been achieved in the treatment of CML due to the development of targeted drugs for tyrosine kinase inhibitors (TKI), but about 20-40% of patients are resistant to therapy. The aim of the study was the detection of exome variants causing resistance to CML therapy. We examined the exomes of 60 CML patients using the Illumina NextSeq® 550 Sequencing System platform. In the group of patients resistant to TKI therapy, loss-of-function variants were revealed in the ASXL1 and DNMT3A genes. Identified variants may be associated with resistance to TKI therapy.

The genome-wide sequencing data of more than 1200 Diffuse Large B-cell Lymphomas (DLBCL) samples of the CBioPortal database for Genomic cancer were analyzed. We also performed our own full-exome sequencing of 7 samples of DLBCL with relapses in the central nervous system (CNS). Characteristics associated with a high level of secondary CNS involvement in lymphoma were selected. Differences were obtained in the BCR/NF-kB genotypes (MYD88, CD79B) and chromatin remodeling system (ARID1A, SMARCA4).

The major research questions: (1) Interaction of TLR9 and AIM2 receptors in MCF7 in response to the action of GC-rich fragments in cell-free DNA (GC-cfDNA); (2) Studying the role of TLR9 and AIM2 receptors in mediating the biological effect of GC-cfDNA on MCF7 cells.

The effects of oxidized extracellular DNA (oecDNA) on genomic DNA damage and activation of transcription of genes regulating DNA repair and apoptosis in human astrocytoma 1321NI cells were studied. OecDNA fragments, 50-100 ng/ml, were added to 1321NI cells for 0.5-24 hours. The levels of oxidative damage and double stranded DNA breaks, BCL and BAX protein expression were determined using antibodies to 8-hydroxy-7,8-dihydroguanosine (8-ohdG), phosphorylated histone γH2AX, BCL2 and BAX proteins and flow cytofluorimetry. The levels of gene expression of BCL2, BAC, BRCA1, BRCA2, TBP (control) were evaluated by real-time PCR. The exposure of 1321NI cells to oecDNA resulted in a 2-4-fold increased levels of 8-ohdG (p <0.01) and 3-3.5-fold increases in double-strand breaks (p < 0.01), whereas the expression of damage repair genes BRCA1 and BRCA2 was enchanced by 3-5 times (p <0.001). In 5-24 hours after exposure to oecDNA cells, the ratio of BCL2/BAX gene expression increased by 3.5-5 times vs. unexposed cell cultures (p <0.001). Therefore, in astrocytoma cells, oecDNA induces both genome rearrangement and adaptive transcriptome reactions followed by activation of an anti-apoptotic path in malignant cells. It is suggested that oecDNA contributes to the accumulation in a residual tumor of mutant clones resistant to treatment thus provoking relapse.

The complex analysis of the follicular thyroid cancer (FTC) hereditary predisposition with using of genealogical, molecular methods and selection indexes is shown the FTC genetic independence; the distribution in the population and families may well be described by means of a variants polygene model with the importance role of genetic factors in determination of disease (88,8 %) and have allowed to assume the presence of interloci interactions in system of its genetic control; positive selection (Δs =0,041) of FTC and association of mutations Р12А and H449H in 2 and 6 exons of gene PPARγ with follicular structure of neoplasias.

Head and neck cancer (HNSC) is a polygenic disease with severe disabling consequences and high mortality.it is the 6th most common cancer in the world. The increase in the incidence in people under 40 years of age, frequent diagnosis at an advanced stage requires the development of prevention measures for this disease. One of the ways to solve this problem is to identify and use in practice biomarkers that detect changes at an early preclinical stage and an approach for assessing the total risk of multifactorial pathology. An approach was developed and risk patterns typical for patients with head and neck cancer were identified. the mathematical model takes into account polymorphisms in 17 genes and shows a sensitivity of more than 16% and a specificity of more than 93%. Validation on a test sample showed 10% sensitivity and 82% specificity, which suggests that the prognosis identifies patients with high risk in the presence of key markers.

A mathematical model of the space-time distribution of a radiomodifying agent - a chemotherapeutic drug - cisplatin with specified physical and chemical properties at the tissue and cellular levels of the biological tissue organization has been developed. The in silico experiment provided data on the kinetics of the intracellular distribution of cisplatin. The model can be adapted to determine the 3D kinetics of nanoparticles, as well as other drugs for the diagnosis or therapy of malignant neoplasms.