The most important objective of modern neuroimaging is comparison of data on genotype and phenotype of brain gliomas. Radiogenomics as a new branch of science is devoted to searching for such relationships based on MRI and PET/CT parameters. The 2021 WHO classification of tumors of the central nervous system poses the most important tasks for physicians in assessment of biological behavior of tumors and their response to combined treatment. The review demonstrates the possibilities and prospects of preoperative MRI and PET/CT with amino acids in assessing the genetic profile of brain gliomas.

Glial cell line-derived neurotrophic factor (GDNF) has a wide range of actions and positively affects viability, proliferative activity and migratory ability of cells in nervous system. That is why GDNF is being considered as a therapeutic molecule in the treatment of neurodegenerative diseases, in particular Parkinson's disease. However, GDNF has the same effect on high-grade glioma cells promoting their growth, resistance to therapy and dissemination. Expression of this factor in tissues and cultures of gliomas is up to five times higher than in intact brain matter. It was revealed that epigenetic modifications in GDNF gene promoter contribute to overexpression. Target suppression of GDNF gene transcription slows down growth of glioma and decreases cell migration. This review is devoted to the effect of GDNF on glioma cells, causes and consequences of its overexpression. Further analysis of expression and function of various GDNF isoforms in glial tumors may be valuable to develop new treatment methods for these dangerous diseases.

The problem of current treatment approaches to brain gliomas is short-term life expectancy in these patients. Apparently, it is required to change treatment approach via analysis of glioma stem cells rather cells with overexpression of marker genes. This review is devoted to similarities and differences between neurogenesis and neuro-oncogenesis characterized with molecular markers (CD133 as an example). The role of tumor stem cells and their relationship with neural stem cells are considered regarding development of glioma. The authors analyzed CD133 as a marker of glioma stem cells. In the future, stem cells will be important target for eradication during target therapy. A single molecular marker cannot characterize tumor stem cells as supported by CD133 studies. A set of molecular markers specific for certain cell type is required, and their combination will provide more accurate establishment of tumor stem cells.

The authors present 2 patients. One of them had typical multifocal primary multiple synchronous wild-type IDH1/2 glioblastoma subtype RTK1, chromosome 7 duplication, homozygous CDKN2A deletion and chromosome 10 deletion. In another patient, the nature of tumors remains debatable. We can talk about either a rare atypical case of metachronous multicentric various glial tumors (oligodendroglioma, IDH1-mutant and 1p/19q-codeleted, WHO grade 2 and RTK2-glioblastoma) or secondary glioblastoma after previous oligodendroglioma arose a year after radiotherapy.

Diffuse midline gliomas are relatively rare in adults. Regardless of age, all diffuse midline gliomas are routinely examined in our Center for the presence of the H3F3A K27M gene mutation. However, we identified IDH-mutant brainstem glioma in a 42-year-old man for the first time.

The paper presents the experience of using DNA methylation status in patients with meningiomas of the craniovertebral junction area in a neurosurgical clinic. A clinical case of combined treatment of a patient with meningioma of the craniovertebral junction and the choice of tactics based on the result of DNA methylation analysis of meningioma are described.

In the latest revisions of the WHO Classification of CNS Tumors, carried out in 2016 and 2021, the traditional histogenetic classification of gliomas is rebuilt on a new molecular genetic basis, according to which diffuse midline glioma with alteration of histone H3 K27 is distinguished as a specific pediatric oncosyndrome. The rationale was the association of this feature of midline gliomas in children with a worse prognosis and the prospective possibilities of targeted therapy. A thematic review of the literature and our own observation of H3 K27M-positive glioma in the area of the right thalamus in a 6-year-old child, which initially had the appearance of pilocytic astrocytoma, recurred three times (within 1.5 years) and underwent tumor progression with anaplastic transformation into diffuse glioma of the glioblastoma type, are presented. The authors are inclined to believe that although the determination of the molecular genetic status of H3 K27 provides important information regarding the probable prognosis, at the same time there is no reason to doubt that histological verification should continue to be the basis of oncological diagnosis.

Evaluation of the frequency of microsatellite instability in gastric adenocarcinomas in patients of the Russian Federation, determination of the relationship of microsatellite instability with clinical and morphological characteristics and the impact on the prognosis.

In the last decade, there has been a «breakthrough» development of scientific approaches to the assay of genomic and immune factors underlying anti-cancer treatment efficiency. The choice of antitumor therapy in practice is increasingly determined by molecular signatures, and not only by the specificity of organ tumor originated from (or by the histological properties of the tumor). An urgent and important scientific and practical task is to study the successful experience of organizing Centers for Personalized Cancer Treatment (CPCT).

Prostate cancer is a clinically heterogeneous disease, and accurate risk stratification of patients is becoming a key clinical task. This is the most common malignant neoplasm and the leading cause of cancer death in men worldwide. Genomic markers include tools and technologies that can predict the probability of an initial positive biopsy, reduce the number of unnecessary repeated biopsies, identify tumors with low, medium and high risk, classify the degree of disease, as well as predict and monitor the clinical response to intervention. Variants of the PTEN gene are of great interest as genetic markers of the risk of developing prostate malignancies.

To study the effect of TERT mutation on overall and relapse-free survival in patients with IDH-negative diffuse astrocytomas grade III (anaplastic gliomas).

Pancreatic ductal adenocarcinoma (PDAC) is the most common and difficult to treat form of pancreas cancer. PDAC and other solid cancers contain both tumor cells and normal connective tissue cells called stromal cells, which are responsible for the excess production of extracellular matrix. It is known that in more than 90% of PDAC tumors and in many other types of cancer, mutations of the KRAS gene are observed, the reciprocal signaling of which has been shown between tumor and stromal cells in vitro. Pancreatic stromal stellate cells are considered precursors of activated or tumor-associated fibroblasts (CAFs), which are an increasing population of cells that proliferate in situ or are recruited into the tumor. CAFs are a heterogeneous population of stromal fibroblasts with different molecular profiles that change during tumorigenesis. Both immunosuppressive and immunosuppressive subsets of CAFs can coexist in the stroma of a single tumor. Based on the heterogeneity of the intertumor stroma, attempts are being made to classify PDAC and predict the course of the disease.

Identification of specific alterations in tumors (as a rule, these are mutations or gene fusions) makes it possible to prescribe targeted drugs of the second line of therapy or, in some cases of inoperable tumors, to observe not only a gradual partial response of the tumor to treatment, but also the removal of these patients from the category of incurable ones. The article describes a new rare type of BRAF::EPB41L2 gene fusion detected in a piloid astrocytoma that developed in the posterior cranial fossa in an 11-year-old boy.

In an experimental study using the CRISPR/Cas9 system, "enhanced" NK cell lines with knockout of CISH, the gene for the CIS protein (a negative regulator of NK cytotoxicity), as well as two lines with a knocked-out β2-microglobulin gene, which provides membrane exposure of MHC class I, were obtained from two parental lines of human natural killers (YT wild type and YT-VAV1^(+) overexpressing the VAV1 cytotoxicity enhancing protein). The knockout efficiency was determined by real-time PCR as well as by flow cytometry with specific antibodies. The resulting CISH^(-/-) or B2M^(-/-) knockout lines were tested for cytotoxicity in primary monolayer cultures of human glioblastoma multiforme. The cytotoxicity of the lines was assessed using a cell analyzer that records the cell index based on cell impedance. YT-CISH^(-/-) has been shown to be significantly more effective than wild-type YT in eliminating primary glioblastoma cells in an in vitro cell monolayer experiment. The cytotoxicity of the YT-VAV1^(+)-CISH^(-/-) and YT-VAV1^(+)B2M^(-/-) lines against glioblastoma cells was the highest, but overall, it did not significantly differ from the initially increased cytotoxicity of the YT-VAV1^(+) line. The lines of NK-like cells obtained may serve as a prototype for the creation of "enhanced" allogeneic and autologous NK- and CAR-NK cells for the immunotherapy of glioblastoma multiforme.

Changes in metabolic pathways are often associated with the development of a wide range of pathologies. Increased glycolysis under conditions of sufficient tissue oxygen supply and its dissociation from the Krebs cycle, known as aerobic glycolysis or the Warburg effect, is a hallmark of many malignant neoplasms. Identification of specific metabolic shifts can characterize the metabolic programming of individual types of tumor cells, the stage of their transformation, and predict their metastatic potential. Viral infection can also alter the metabolism of cells to support the process of viral replication. Infection with human immunodeficiency virus type 1 (HIV-1) is associated with an increased incidence of various cancers, and for some viral proteins a direct oncogenic effect was demonstrated. In particular, we showed that the expression of HIV-1 reverse transcriptase (RT) in 4T1 breast adenocarcinoma cells increases the tumorigenic and metastatic potential of cells in vitro and in vivo by a mechanism associated with the ability of RT to induce reactive oxygen species in cells (ROS). The aim of this work was to study the molecular mechanism of this process, namely the effect of HIV-1 RT on the key metabolic pathways associated with tumor progression: glycolysis and mitochondrial respiration. Expression of HIV-1 RT had no effect on the glycolysis process. At the same time, it led to an increase in mitochondrial respiration and the level of ATP synthesis in the cell, while not affecting the availability of the substrates, carbon donors for the Krebs cycle, which excludes the effect of RT on the metabolic enzymes of cells. Increased mitochondrial respiration was associated with restoration of the mitochondrial network despite the RT-induced reduction in mitochondrial mass. Increased mitochondrial respiration may increase cell motility, which explains their increased tumorigenicity and metastatic potential. These data are important for understanding the pathogenesis of HIV-1 infection, including the stimulation of the formation and spread of HIV-1 associated malignancies.

Human cytomegalovirus (HCMV) DNA and proteins are often detected in malignant tumors, warranting studies of the role that HCMV plays in carcinogenesis and tumor progression. HCMV proteins were shown to regulate the key processes involved in tumorigenesis. While HCMV as an oncogenic factor just came into focus, its ability to promote tumor progression is generally recognized. The review discusses the viral factors and cell molecular pathways that affect the resistance of cancer cells to therapy. CMV inhibits apoptosis of tumor cells, that not only promotes tumor progression, but also reduces the sensitivity of cells to antitumor therapy. Autophagy was found to facilitate either cell survival or cell death in different tumor cells. In leukemia cells, HCMV induces a "protective" autophagy that suppresses apoptosis. Viral factors that mediate drug resistance and their interactions with key cell death pathways are necessary to further investigate in order to develop agents that can restore the tumor sensitivity to anticancer drugs.

Viruses are now recognized as bona fide etiologic factors of human cancer. Carcinogenic viruses include Epstein-Barr virus (EBV), high-risk human papillomaviruses (HPVs), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus type 1 (HIV-1, indirectly), and several candidate human cancer viruses. It is estimated that 15% of all human tumors worldwide are caused by viruses. Tumor viruses establish long-term persistent infections in humans, and cancer is an accidental side effect of viral replication strategies. Viruses are usually not complete carcinogens, supporting the concept that cancer results from the accumulation of multiple cooperating events, in which human cancer viruses display different, often opposing roles. The laboratory mouse Mus musculus is one of the best in vivo experimental systems for modeling human pathology, including viral infections and cancer. However, mice are unsusceptible to infection with the known carcinogenic viruses. Many murine models were developed to overcome this limitation and to address various aspects of virus-associated carcinogenesis, from tumors resulting from xenografts of human tissues and cells, including cancerous and virus infected, to genetically engineered mice susceptible to viral infections and associated cancer. The review considers the main existing models, analyzes their advantages and drawbacks, describes their applications, outlines the prospects of their further development.

Immunofluorescent method by flow cytometry was used to quantify the expression of the tumor-associated protein βIII-tubulin (TUBB3) in the tissue of urothelial bladder cancer and visually normal mucosa (56 samples in total). The expression of the marker was detected in 100% of cases, and heterogeneity of the TUBB3 expression level both in tumor tissue and in "normal" mucosa was revealed. The level of TUBB3 in the "normal" mucosa did not depend on the distance from the tumor (1 cm or more than 3 cm) and, on average, it was lower than in the tumor tissue (21.8 ± 10.8% and 24.9 ± 13.2% vs 35.2 ± 12.4%; p = 0.04 and 0.005, respectively). An increase of the TUBB3 expression in the tumor and in the "normal" mucosa was revealed in muscle invasive bladder cancer compared to non-muscle invasive bladder cancer. Therefore, in urothelial bladder cancer, the tumor-associated protein TUBB3 is a molecular marker of bladder mucosa involvement in the malignancy process and predicts the risk of tumor muscle invasion, which may influence indications for early cystectomy.

Increased expression levels of the Oct-1 transcription factor is considered to be one of the key markers of poor cancer prognosis. In addition to the ubiquitous Oct-1A isoform, which is found in all cells, there also exists a tissue-specific Oct-1L isoform, which is expressed in hematopoietic cells. Oct-1L increases cell resistance to different stresses and also regulates the expression of genes controlling differentiation of hematopoietic and immune system cells. The tissue-specific Oct-1L isoform levels are significantly increased in the B-cell lymphoblastoma Namalwa and Raji lines and the T-cell lymphoblastoma Jurkat line compared to normal B and T cells. Apparently, aberrant Oct-1L overexpression not only enhances stress resistance but also leads to the disruption of developmental pathways in the cells promoting their malignant transformation. We report here that targeted suppression of the tissue-specific Oct-1L isoform expression reduces the proliferation rate of Namalwa B-lymphoblastic Burkitt's lymphoma cells, significantly increases cell death rate under hypoxic conditions, and makes cells more sensitive to chemotherapeutic agents such as docetaxel and doxorubicin. These results indicate that targeted therapy aimed at the suppression of the Oct-1 isoforms with increased expression levels in tumor cells rather than the total Oct-1, thus avoiding the traumatic effects of total Oct-1 knockdown, may be promising. Selective suppression of Oct-1 isoforms is a promising strategy in the treatment of lymphoid tumors and may contribute to mitigating the disease course and increasing survival rates in cancer patients.

Colorectal cancer (CRC) is a malignancy featured by a poor overall survival and a high recurrence rate, whereas the biomarkers for CRC remain to be investigated. Herein, it was found that lysophosphatidylcholine acyltransferase 1 (LPCAT1) was highly expressed in CRC, and LPCAT1 overexpression significantly promoted CRC cell proliferation, while it was reversed by LPCAT1 depletion. In addition, HECT domain-containing 2 (HECTD2) protein was determined as a post-translational mediator of LPCAT1 because HECTD2 co-immunoprecipitated with high ubiquitinated LPCAT1. Furthermore, upregulated LPCAT1 rescued the impairment of CRC cell proliferation caused by HECTD2 overexpression. In conclusion, our findings supported HECTD2/LPCAT1 axis as a potential prognostic biomarker in CRC.