to determine molecular diagnostics routine for different tissue samples in angioimmunoblastic T-cell lymphoma.

Aim of the issue was to compare clinical characteristics and treatment results of patients with follicular lymphoma (FL) with translocations involving loci of c-MYC/8q24, BCL2/18q21 and/or BCL6/3q27 genes and patients with high - grade B-cell lymphoma [High - grade B-cell lymphoma (HGBL), double - hit (DH)]. Materials and methods. Since 2004 to 2017 years in National Research Center for Hematology 12 patients with high - grade B-cell lymphoma double - hit (HGBL DH) and 6 FL patients with translocations involving c-MYC and BCL2 and/or BCL6 had been treated. We performed a comparative analysis of clinical characterisctics in both groups. As primary endpoints was assessed frequency of complete remission (CR) or progressive disease (PD); as secondary endpoints - overall (OS) and event - free survival (EFS). Results. 5 patients with HGBL DH had c-MYC/BCL6, 7 - c-MYC/BCL2 rearrangements; 2 patients with FL had c-MYC/BCL2, 3 - c-MYC/BCL6, 1 - c-MYC/BCL2/BCL6 rearrangements. FL was represented by grade 3A in 2, grade 3B - in 4 cases, 3 of them had large - cell transformation. In HGBL DH and FL patients had no significant differences in clinical characteristics. The majority of patients had a widespread tumour, increased LDH activity, high frequency of extranodal and bone marrow involvement. Ki-67 expression level was lower in patients with FL (p.

To determine a diagnostic algorithm for detecting translocation of the ALK gene and its frequency in the Moscow region.

Interferons (IFN) and IFN inducers are effective in suppressing viral reproduction and correcting of the innate immunity mechanisms. The aim of the study was to test the hypothesis of the possible involvement of the IFN inducer CelAgrip (CA) as an activator or suppressor of antiviral effects in Burkitt's lymphoma (LB) cell cultures with different ability to produce Epstein-Barr virus antigens (EBV).

Molecular studies have shown that viruses appeared in the early stages of the evolution of life. For millions of years, viruses have evolved by changing old and acquiring new sequences in their RNA or DNA. It is assumed that most viruses have common ancestors. Such an ancestor, an ancient strain, probably existed for Epstein-Barr virus (EBV) as well.

Currently, new directions in cancer therapy are actively developing, one of which is oncolytic immunotherapy. This approach would be to use of viruses as cancer specific cytolytic agents capable of stimulating both the tumor-specific and non-specific immune response. The objective paper was obtain a recombinant vaccinia virus containing genes encoding immunostimulating molecules and study oncolytic and immunostimulating properties of recombinant virus.

Certain subtypes of acute myeloid leukemia occur as a result of the cooperation of several events these are, the formation of fusion genes as a result of chromosomal rearrangements, which leads to the disruption of cell differentiation, and the emergence of mutations that enhance cellular proliferation by activating intracellular signaling pathways. High-throughput sequencing methods reveal characteristic mutation spectra in leukemia associated with different chromosomal disorders. However, the role of mutation events in malignant cell transformation processes remains obscure. We searched for driver mutation events in leukemic cells containing the chimeric CBFB-MYH11 gene, which results from inversion of chromosome 16. Using target enrichment, the coding regions of 84 genes in genomes of 12 children with acute myeloid leukemia with inv(16) were investigated. Somatic mutations have been found in the genes of the proteins of intracellular signaling cascades mediated by receptor tyrosine kinases, such as KIT (41%), NRAS (25%), KRAS (17%), and FLT3 (8.3%). Comparative analysis of samples at the time of diagnosis and during remission was used to assess the role of mutations in the pathogenesis of the disease. Previously undescribed mutations in the KDM6A, NOTCH1, and IDH1 genes, which may be involved in leukemogenesis processes have been identified.

DNA hypermethylation and mutations are key mechanisms for the downregulation of tumor suppressor genes. NotI-microarrays allowed us to detect hypermethylation and/or deletions in 180 NotI sites associated with 188 genes of human chromosome 3, in 24 paired (tumor/normal) colon samples. The most frequent aberrations (in more than 20% of tumor samples) were detected in the promoter regions of 20 genes. Expression and promoter methylation of these genes were analyzed using the data for paired colon samples from The Cancer Genome Atlas project. Three genes - ALDH1L1, PLCL2, and PPP2R3A - revealed a more than two-fold average decrease in expression and a negative correlation between mRNA level and promoter hypermethylation. The expression of these three genes was then evaluated in 30 paired colon samples by quantitative PCR. Frequent (in more than 60% of cases) and significant (5-9-fold on average) mRNA level decrease was found for each of the genes in the tumor samples. The results indicate a suppressor role of the ALDH1L1, PLCL2, and PPP2R3A genes in colon cancer, as well as functional significance of hypermethylation in the downregulation of these genes.

It was found that the proportion of microRNA genes inactivated by methylation of regulatory CpG islands is several times higher than the genes encoding proteins, which increases their attractiveness as promising markers of cancer. The aim of this work is to evaluate the clinical significance of methylation of 13 tumor-associated microRNA genes (MIR-124a-2, MIR-124a-3, MIR-125-B1, MIR-127, MIR-129-2, MIR-132, MIR-137, MIR-203a, MIR-34b/c, MIR-375, MIR-9-1, MIR-9-3, MIR-339) in 26 patients with ovarian cancer. Methylation level was evaluated by the method of methylation-specific PCR in real time. The data obtained in primary tumors (26), histologically unchanged ovarian tissues (15) and peritoneal metastases (19) were compared using a number of statistical programs. For all 13 genes, an increase in the level of methylation was revealed during the transition from unchanged tissue to primary tumors and further from primary tumors to peritoneal metastases; moreover, in the genes MIR-203a, MIR-375 and MIR-339, the level of methylation in metastases increased most significantly (in 2 and more times). A correlation was observed for the first time, showing a consistency between the increase in methylation level in some miRNA pairs, for example, MIR-129-2/MIR-132 (rs> 0,7; p<0,0001), both in primary tumors and in metastases. An analysis of microRNA gene methylation in clinical samples of ovarian cancer showed a correlation between the observed molecular changes both with the initial stages of tumor formation and with the progression and dissemination of ovarian cancer, with the presence of metastases in a large omentum and with the appearance of ascites. The revealed dependencies deepen the understanding of the mechanism of peritoneal metastasis and can be used to select new diagnostic and prognostic markers of ovarian cancer.

In hepatocellular carcinoma (HCC), the presence of cancer stem cells (CSCs) have been linked to drug resistance, epithelial-mesenchymal transition (EMT), and cancer relapse. This study investigates the expression profile of ZEB1, ZEB2, ABCG2 in HCC-CSCs, and the role of EMT promoter ZEB2 in cells treated with resveratrol. The expression of ZEB1, ZEB2 and ABCG2 transcripts were analyzed in CD133^(+)/CD44^(+) cells isolated from the PLC/PRF/5 cell line. ZEB2-dependent ABCG2 gene expression and the effects of resveratrol on proliferation, cell cycle and apoptosis were explored in SNU398 cell clones. An inverse correlation between ZEB1/ZEB2 and ABCG2 levels were observed both in CSCs and in ZEB2-knock-down cells. The resveratrol treatment significantly decreased cell viability, while promoting cell cycle arrest in ZEB2-independent manner. Interestingly, resveratrol-treated cells with low levels of ZEB2 were resistant to apoptosis. The interplay of expression levels of ABCG2 and ZEB family EMT transcription factors may play a role in establishing CSC-like phenotype in HCC cells resistant to resveratrol.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor prognosis and high mortality. The aberrant expression or alteration of microRNAs (miRNAs) contributes to the development and progression of cancer. Studies have shown that miR-455 plays a regulatory role in the development of HCC. Therefore, in the present study, the role of miR-455 was analyzed in HepG2 cells proliferation and apoptosis using MTT and flow cytometry methods. Binding sites were predicted by bioinformatics and luciferase assay was used to verify the target relationship between miR-455 and RhoC-encoding gene RHOC. After that, the effects of miR-455 on RHOC and its product RhoC, were explored by qPCR and Western blotting. As PTEN is a key tumor suppressor gene in HCC, and Bcl-2 and Caspase 3 are important indication of apoptosis, expression levels of PTEN, Bcl2 and Caspase 3 proteins were determined in cells overexpressing RhoC. We show that miR-455 promotes HepG2 cells apoptosis and inhibits proliferation. Bioinformatics analysis and luciferase assay indicate that specific recognition sites for miR-455 are within the RhoC 3'-UTR. Luciferase activity was significantly lower in the cells co-transfected with miR-455 mimics and RhoC-WT (p < 0.01) as compared to that in control cells, pointing that RHOC gene is, indeed, targeted by miR-455. RHOC mRNA was significantly reduced after miR-455 transfection in HepG2 cells. In addition, we show that RhoC could activate the HCC cells proliferation ability and inhibit apoptosis rate (p < 0.01), and decrease expression of PTEN and Caspase 3 (p < 0.01), while upregulating levels of Bcl2. In conclusion, our study indicates that miR-455 plays a suppressive role in HCC development by targeting RhoC-encoding mRNA.

PTTG1 (vertebrate securin) is a separation inhibitor and regulates DNA repair and transcription. The protein is predominantly expressed in the second half of the S phase and at the G2 stage. With the onset of anaphase, securin is ubiquitinated by the APC/C complex and degraded rapidly. Increased expression of PTTG1 is associated with enhanced tumor cell growth and metastasis. Recently, we found a short securin isoform lacking the main APC/C recognition site (D-box) and the DNA-binding domain encoded by exons 3 and 4. The mRNA level of the short isoform in unsynchronized cells is 0.4-2% of the full-length one. We reported earlier on the ability of the short PTTG1 isoform to activate some of the genes controlled by the full-length protein. In this work, groups of genes, whose expression is altered by the action of the short and complete securin isoforms, were determined using RNA sequencing. Groups of genes whose mRNA levels are regulated by both protein isoforms and only one of the isoforms were identified. For a more detailed study of the effect of securin isoforms on the transcriptional program of cells, the NFYB gene, encoding the NF-Y transcription regulator subunit, was chosen. Our data showed that with overexpression of the short isoform, the level of NFYB mRNA decreased 2.4 ± 0.7 times, while the complete isoform did not significantly affect the expression of NFYB. 2.2-fold suppression of the short isoform of securin led to an increase in the expression of NFYB mRNA by 2.7 ± 0.3 times. Moreover, the mRNA expression of full-length securin increased by 2.7 ± 0.4 times. Since NFYB is associated with the PTTG1 promoter region, we suggest that the short isoform may be involved in regulation of the expression of the main isoform of securin by changing the level of this transcription factor. Since NFYB and PTTG1 are involved in the development of tumors and the formation of drug resistance, we assume that the short isoform of securin may play an important role in these processes. Thus, we showed the functional significance of the minor short isoform of securin.

The lack of specific symptoms for the early detection of gastric cancer leads to the fact that it is often diagnosed at a late stage, when the prognosis is unfavorable. The analysis of molecular markers in addition to standard diagnostic procedures is a promising approach for improving the preoperative diagnosis of both gastric cancer and precancerous changes in the mucosa. Therefore, the aim of our study was to analyze the diagnostic significance of using miRNA expression to diagnosis gastric cancer and precancerous conditions (dysplasia) in histological material. In this work, 122 samples of archival histological material in the form of paraffin blocks were used: 34 samples of gastric adenocarcinoma, 54 samples of gastric ulcers with dysplasia and 34 samples of normal gastric mucosa obtained from patients after bariatric surgery. The expression level of miRNA-145-5p, -150-5p, -20a-5p, -21-5p, -31-5p, -34a-5p, -375 was determined using real-time RT-PCR. Samples were stratified into different groups using the C-RT decision tree algorithm. All miRNAs, except miRNA-20a, were included in the decision tree, which allows stratification of samples for normal mucosa, dysplasia, and gastric cancer. Normal mucosa can be distinguished from gastric cancer only by miRNA-34a, -21, -375. Diagnostic characteristics for the detection of dysplasia: specificity - 97%, sensitivity - 87%; for the detection of gastric cancer: specificity - 91%, sensitivity - 93%. The sufficiently high values of the diagnostic characteristics for detecting dysplasia of the gastric mucosa and gastric cancer obtained in our study indicate the possibility of using expression data of a small amount of miRNAs for the effective separation of samples with tumor and precancerous changes in the stomach tissue.

The colorectal cancer is considered as the third most common malignant disease in the world. During last decade, the problem of colorectal cancer became especially urgent conditioned not only by increasing of number of metastatic tumors of colon and rectum, but also by implementation of high-tech methods of treatment that significantly improved the results of five-year survival period. Along with success of therapy, understanding of genomics of colorectal cancer and owing to extensive application of next generation sequencing, the opportunity of optimal choice of treatment options was offered.

Denys-Drash syndrome is characterized by a triad: nephropathy, a 46, XY disorder of sex development, and nephroblastoma with mutations in the gene WT1. A clinical case of a patient with a bilateral metachronous Wilms' tumor, a 46, XY disorder of sex development in the form of a scrotal hypospadias and bilateral abdominal cryptorchidism, without nephropathy with a mutation in 7 exon of gene WT1 is presented in the article. The child underwent left-sided nephrectomy, lower pole right partial nephrectomy, bilateral orchiopexy and two-stage correction of hypospadias. After 7 years from the start of treatment and 3 years after the last procedure, the childs condition has been assessed as satisfactory. The presented case, according to the analysis of literature, has not been previously described, therefore, it currently remains as "de novo" and requires further observation.

The development of new research methods significantly changed our views on the role that the 3D organization of the genome plays in its functional activity. It was found that the genome is subdivided into structural-functional units that restrict the area of enhancer action at the level of spatial organization. Spatial reconfiguration of an extended genomic fragment was identified as a potential mechanism that activates or represses various genes. Accordingly, a distorted spatial organization of the genome often causes various diseases, including cancer. All these observations contributed to the emergence of 3D genomics as a new avenue of research. The review summarizes the most important discoveries in the field of 3D genomics and discusses the directions of its further development.

as shown in previous studies, mutations in the BRCA1/2 and CHEK2 genes are associated with worsened long-term results of the definitive treatment for localized prostate cancer (PCa).

Studies of the last decade have demonstrated that the morphological and immunophenotypic patterns of adrenocortical carcinoma (ACC) have a high heterogeneity in both the occurrence of various tumors and the development of a solitary tumor. Carcinogenesis of ACC, like most neoplastic processes, is associated with mutations in at least 15 driver genes, with a wide range of chromosomal aberrations, epigenomic changes, and alterations of the microRNA profile. According to the literature, isolated genetic damage is also insufficient for the manifestation of the malignant phenotype of adrenocortical cells. Knudson's two-hit hypothesis is implemented in at least germline mutations: the development of ACC requires a second genetic event occurring in somatic cells, which leads to inactivation of the second allele of the gene. ACC is an extremely heterogeneous disease, which determines the complexity of differential diagnosis with benign adrenocortical tumors and that of prediction of the clinical course. Another no less important issue is the lack of valid predictors for the efficacy of mitotane, the use of which may be associated with severe adverse effects.

The paper describes 2 cases of immature ovarian teratoma with elements of nephroblastoma (ICD-0 code 9080/3) in patients aged 61 and 70 years. Microscopic examination revealed that both cases had blastemal cells with scant cytoplasm and basophil nuclei sticking together. Epidermal, glandular, rhabdomyoblastic, chondroid, bone, neuroectodermal, and histiocytic components were determined. Papillary and glomeruloid structures and primitive tubules were immured in the sarcomatous stroma. Immunohistochemical studies showed a strong reaction with Wilms tumor 1 (WT1), paired box gene (PAX-2), cytokeratin 7, desmin, smooth muscle actin, and α-1 antitrypsin. The recurrent tumors displayed a 1.8- to 6.1-fold increase in the level of p53. At the same time, the molecular genetic study revealed p53 gene mutation. In both cases, serous ovarian cystadenocarcinoma was misdiagnosed, ineffective chemotherapy was performed, and a recurrence occurred. The literature review revealed only 8 such cases.

Oral cavity squamous cell carcinoma (OC-SCC) is the most common and aggressive malignancy of the oral cavity. Recent studies have revealed infections with human papilloma virus (HPV) as an additional risk factor for oral squamous cell carcinoma development, while distinguished role of Epstein-Barr virus (EBV) remains still uncertain. However, the evidence for association between virus infection and risk of oral squamous cell carcinoma is controversially and varies significantly by geographic regions and race.