Background. Diffuse brainstem tumors account for 10-20% of all brain tumors in children. These neoplasms are the leading cause of death in pediatric neuro-oncology. There are no effective treatments for this disease. Overall survival rarely exceeds 1.5-2 years.

Glioblastoma or grade IV glioma is characterized by extremely poor prognosis. Resistance to radio- / chemotherapy and recurrences are associated with tumor stem cells. Transmembrane protein CD133 is considered a potential marker of tumor stem cells. To overcome the limitations of detecting cellular CD133 by antibodies, potential of aptamers (nucleic acid-based molecular recognition elements) is being explored. To obtain reproducible results, it is necessary to study the interaction of fluorescent aptamers to CD133 with standard cell lines and cell cultures derived from patient tumors using various methods.

There is only a limited number of studies devoted to the molecular genetic status of patients with iris melanoma.

This study aimed to investigate the plasma expression levels of microRNA-223, microRNA-27b, and microRNA-155 in patients with choroidal melanoma (CM) T1-2N0M0 before and after brachytherapy (BT).

 Multiple endocrine neoplasia syndrome type 1 (MEN-1) is a rare, autosomal dominant disorder resulting from inactivating mutations in the MEN1 gene. It demonstrates high penetrance, with the "classic triad" of manifestations comprising primary hyperparathyroidism (PHPT), gastrointestinal neuroendocrine neoplasms (NEN), and pituitary adenomas. Diagnosis relies on clinical, familial, and genetic criteria. However, significant phenotypic variability and the lack of a clear genotype-phenotype correlation complicate early diagnosis.

To create a prognostic scale for overall survival in grade 4 astrocytomas based on molecular biological data.

Thyroid nodules in children are relatively rare; the risk of malignancy is considerably higher compared to adults. The optimal extent of surgery, the indications for radioactive iodine therapy (RAI), and the role of molecular genetic testing in children with thyroid carcinoma remain a matter of debate.

Von Hippel-Lindau syndrome (FHL) is a rare autosomal dominant disease that leads to the formation of multiple organ tumor syndrome. The pathology is primarily caused by the inactivation of the VHL gene, which is located on chromosome 3 (3p25/26) and encodes ubiquitin ligase, which destroys hypoxia-induced factor-1α (HIF-1α). The genetic defect leads to the accumulation of HIF-1a protein, activating key carcinogenic pathways, and activated cytokines cause abnormal proliferation of tumor cells and oncogenesis. To date, more than 500 mutations have been registered in VHL. FHL syndrome is characterized by various tumors, including hemangioblastomas of the retina and central nervous system, pheochromocytomas, clear cell renal cell carcinoma, cystic adenoma and others. In the presented clinical description, pheochromocytoma was initially diagnosed in the patient's mother, and 2 months later in the eldest son. Subsequently, the results of a molecular genetic study made it possible to verify the diagnosis, since in the gene in exon 3 of VHL, a single nucleotide was replaced in the heterozygous state of C.500 G>A, leading to the replacement of the amino acid p.R167Q. Identification of the VHL gene mutation required genetic counseling of all family members, during which a similar mutation was identified in the younger brother. Surgical treatment is the main method of treating FHL syndrome, but advances in genetic research technologies provide new opportunities for the treatment of tumors associated with this syndrome.

TRPS1 (Tricho-rhino-phalangeal syndrome type 1) - a transcription factor of the GATA family, has recently emerged as a promising immunohistochemical marker for breast cancer. This review summarizes current data on the diagnostic, prognostic, and potential therapeutic relevance of TRPS1, as well as its molecular functions and expression patterns across different breast cancer subtypes. TRPS1 demonstrates high sensitivity, including in diagnostically challenging cases such as triple-negative and poorly differentiated carcinomas, where traditional markers (GATA3, mammaglobin) may be absent or weakly expressed. The advantages of TRPS1 in the differential diagnosis of metastatic lesions and its possible role in prognostic panels are highlighted. Methodological limitations of the using marker, standardization needs and future perspectives for clinical implementation are also discussed in article.

The genes of mismatch repair system (MMR) are responsible for correcting errors in DNA replication. MMR defects (dMMR) lead to mutations in microsatellites - repetitive nucleotide base sequences - resulting in microsatellite instability (MSI). Determination of dMMR/MSI status in tumors is an important factor for the development of patient management tactics, as the dMMR/MSI phenotype serves as both a marker of favorable prognosis and a predictor of response to immunotherapy in tumors of many localizations. MMR status is assessed via immunohistochemistry (IHC) on histological material. However, in some cases heterogeneity of intratumoral MMR protein expression (MMR heterogeneity) becomes an obstacle to this. MMR heterogeneity (areas of weak/absent staining on the background of normal expression) is poorly studied, especially in gastric cancer, in contrast to colorectal cancer and endometrial cancer. The lack of a methodology for interpreting this phenomenon leads to significant difficulties in stratifying patients who are indicated for dMMR/MSI status determination. The article systematizes current data on MMR heterogeneity in gastric cancer and tumors of other localizations, discusses molecular mechanisms, clinical significance and recommendations to overcome diagnostic limitations.

This study analyzes the modern (2021) WHO classification of lung tumors and reviews publications in Russian and English from databases including PubMed, Google Scholar, ClinicalTrials.gov, eLibrary, and CyberLeninka. The aim of this review is to identify key changes in the 2021 WHO classification compared to the 2015 edition and assess their significance for the diagnosis and personalized treatment of non-small cell lung cancer. Special attention is given to the handling of small biopsy specimens, which requires an integrated approach involving morphological examination, immunohistochemistry, and molecular genetic testing.

To evaluate changes in gene expression activity during preoperative testing for tumor hormone sensitivity to aromatase inhibitors and tamoxifen in postmenopausal women with ESR+/HER2- breast cancer.

To improve the stratification algorithm for aggressive B-cell lymphomas in children based on the analysis of genetic changes in the genes TP53, MYC, BCL2, BCL6 and the long arm of chromosome 11 (11q).

Differentiation of high-grade gliomas (WHO grades III and IV) is still a pressing issue despite advances of molecular biology in tumor stratification. Even with a comprehensive approach to differential diagnosis, uncertainty sometimes arises in classifying a glioma into a particular grade. This can complicate prognosis and selection of appropriate treatment.

Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors that originate in the parasympathetic paraganglia of the head and neck. The diagnosis of these tumors is challenging, and the therapeutic options are limited. The study of HNPGLs is fraught with challenges at every stage. One of the main problems is the absence of HNPGL cell lines in cell repositories, which is associated with the difficulty of their culturing and low division rate. In this regard, neither functional nor preclinical studies are available for this category of tumors. This significantly slows down the study of the molecular mechanisms of HNPGL pathogenesis and the development of effective therapeutic approaches. Here, we investigated the molecular genetic characteristics of the primary HNPGL culture. Using the single-cell RNA sequencing method, expression patterns were analyzed, and cell types were annotated. The results demonstrated that the HNPGL primary culture cells were optimally divided into three clusters and had different degrees of differentiation, expressing neural tissue cell and stem cell markers. Exome sequencing revealed genetic abnormalities in the HNPGL culture, including mutations in the IGSF3, DHH, EXOSC8, SERPINA1, TYR, and NQO1 genes, aneuploidy, as well as multiple chromosomal duplications and deletions. These results enhance our knowledge of the molecular genetic features of successfully cultured HNPGL tumor cells.

The epidermal growth factor receptor (EGFR) is among the research subjects of most interest and remains genuinely attractive due to its key role in regulating the main conserved signaling pathways responsible for cell growth, survival, and proliferation. Dysregulation of the signaling pathways leads to cell malignant transformation, tumor progression, and metastasis. Therefore, EGFR is considered as one of the main targets for anticancer drug development. Although several generations of novel anti-EGFR drugs have been successfully developed, acquisition of drug resistance and the mutation status of the downstream effector protein KRAS significantly reduce the tumor response to therapy. The review focuses on the current approaches to anti-EGFR therapy. Drugs designed to block the EGFR-mediated signaling are described, including monoclonal antibodies, tyrosine kinase inhibitors, and immunotoxins. Mechanisms of acquired resistance to anti-EGFR therapy are discussed, and combination treatment strategies are proposed to improve the efficacy of the available drugs. Finally, promising antitumor agents, including ribonucleases (RNases) of various origins, are considered.

Colorectal cancer remains one of the leading causes of cancer-related mortality, highlighting the importance of optimizing approaches for its early diagnosis and therapy. One promising area in this field is the investigation of the role of the gut microbiome in the initiation and progression of colorectal cancer. This review examines three principal hypotheses explaining the contribution of microbiota to carcinogenesis: the "Alpha-bug", the "Keystone pathogen", and the "Driver-Passenger" models. We analyze data on the mechanisms of microbiota-tumor cells interactions, including the induction of inflammation, genotoxicity, and disruption of the intestinal barrier function. Findings are also presented indicating that certain microorganisms previously considered markers of the advanced stages may possess pro-oncogenic properties, thereby refining existing carcinogenesis models. Overall, the data suggest that the microbiota and its dysbiotic alterations can be considered potential targets for colorectal cancer diagnosis and therapy.

The aim of the study was to analyze genomic combinations of four SNPs-rs4430796 (HNF1B), rs1859962 (CASC17), rs1447295 (CASC8), and rs6983267 (CCAT2) - associated with prostate cancer (PCa) in urological patients, including those with benign prostatic hyperplasia (BPH), PCa, and urolithiasis (UL).

Breast cancer remains one of the leading causes of cancer mortality among women, and the study of epigenetic mechanisms is an important task of molecular oncology in breast cancer. In this study, we analyzed the expression levels of eight microRNAs (miR-125b-5p, -127-5p, -129-5p, -132-3p, -148a-3p, -193a- 5p, -24-2-5p, and -34b-3p) and methylation of promoter regions of seven microRNA genes in a representative set of 40 and 70 paired samples of tumor and normal breast tissue, respectively, and showed hypermethylation of promoter regions of seven genes and a statistically significant decrease in the expression levels of eight microRNAs in tumors. For three genes (MIR125B-1, MIR129-2, MIR148A), inverse relationships between methylation and expression (rs < -0.5) were revealed, indicating their possible epigenetic regulation. Statistically significant positive correlations of expression levels were revealed for seven pairwise combinations of miRNAs, suggesting their coordinated functioning. Indeed, for the pairs miR-127-5p/miR-125b-5p, miR-148a-3p/miR-125b-5p, miR-148a-3p/miR-132-3p, and miR-34b-3p/miR-193a-5p, common mRNA targets and involvement in biological processes, including pathways associated with epigenetic regulation, proliferation, and metastasis, were revealed. The miRNA-mRNA regulatory network constructed involving DNMTs and EZH2 highlights their potential role in breast cancer progression and demonstrates diagnostic and prognostic significance.

Pancreatic Ductal AdenoCarcinoma (PDAC) is one of the most therapy-resistant tumors. Cultured cells originating from different stages of PDAC development are characterized by different levels of expression of a number of transcription factors. In particular, poorly differentiated high-grade PDAC cells are characterized by increased expression of ZEB1 gene encoding multifunctional transcription factor ZEB1, one of the main regulators of epithelial-mesenchymal transition. By the method of Circular Chromosome Conformation Capture (4C-seq) we studied the spatial organization of chromatin of regulatory region of ZEB1 gene in cultures of highly differentiated PDAC cells (Capan2) with low level of ZEB1 expression and poorly differentiated PDAC MIA PaCa2 cells with a high level of expression of this gene, and compared it with the chromatin organization of KLF5 gene. The number and distribution of contacts of the ZEB1 regulatory region with other chromatin regions are similar in these cell types and differ significantly from the pattern of distribution of contacts characteristic for KLF5 gene studied earlier. In Capan2 cells, the contacts of the regulatory region of the ZEB1 gene are tend to locate in regions with an increased level of H3K27ac modification, whereas in MIA PaCa2 cells these contacts are predominantly located in regions with a decreased level of H3K27ac. Consequently, the probability of contact of distant chromatin regions is primarily determined not by the degree of chromatin openness/activity of this region. To explain the data obtained, we assumed that the main regulator of the ZEB1 gene transcription level in the studied cells is a transcriptional repressor, whereas for the KLF5 gene main regulator is a transcriptional activator. According to a number of properties, one of the possible candidates for the role of this repressor may be the product of the ZNF438 gene. In addition, we have characterized a number of regions in contact with the ZEB1 promoter that are specific for MIA PaCa2 cells and contain potential regulators of this gene activity.