[Verification of the diagnosis of supratentorial ependymomas by real-time PCR]. / Verifikatsiya diagnoza supratentorial'nykh ependimom metodom PTsR v rezhime real'nogo vremeni.

BACKGROUND: Differential diagnosis of supratentorial ependymomas is of particular difficulty in neurooncology due to nonspecific clinical and radiographic findings, a rare seen «classic¼ morphological picture, and a nonspecific immunophenotype. Thanks to molecular genetic methods, in particular real-time PCR, it has become possible to verify supratentorial ependymomas and identify their molecular group, on which further prognosis depends. OBJECTIVE: To develop a set of molecular genetic tests based on real-time PCR to verify supratentorial ependymomas. MATERIAL AND METHODS: 56 tissue samples were collected from patients with supratentorial ependymomas, WHO Grade II, and anaplastic ependymomas, WHO Grade III. We developed primers and fluorescent TaqMan probes for real-time PCR analysis to detect the ZFTA::RELA, ZFTA::MAML2, ZFTA::NCOA2, ZFTA::MAML3, YAP1::MAMLD1, and YAP1::FAM118B gene fusions. For immunohistochemical analysis, monoclonal rabbit anti-NF-kb p65 antibodies (HUABIO, China) were used, the study was carried out on AutostainerLink 48 immunostainer (DAKO, Denmark). RESULTS: Real-time PCR was able to verify the diagnosis for 69.9% (n=39) of samples and classify them into molecular groups of ZFTA- or YAP1-positive supratentorial ependymomas. Immunohistochemically it was possible to verify 58% (n=29) ependymomas. CONCLUSION: Diagnosis by real-time PCR is a relatively fast, accessible and easily interpreted method that allows verification of the molecular group in 70% of cases of supratentorial ependymomas without the use of additional methods.

[Astrocytoma with 1p19q codeletion]. / Astrotsitoma s kodeletsiei 1p19q.

Using the example of a recurrent tumor with a 10-year follow-up, the authors show that mutation of the IDH1/2 genes in astrocytomas is not always an early event in the pathogenesis of glioma, that in rare cases a 1p19q codeletion can be found in astrocytomas, and that IDH-mutant tumors can occur in childhood.

[Chordoid gliomas of the third ventricle]. / Opyt lecheniya khordoidnykh gliom III zheludochka.

BACKGROUND: Chordoid glioma is a rare slow-growing tumor of the central nervous system. Available world experience includes no more than 200 cases (lesion of the third ventricle in absolute majority of cases). Recognition and treatment of chordoid glioma are currently difficult problems due to small incidence of this disease. OBJECTIVE: To describe clinical manifestations and surgical treatment of chordoid glioma of the third ventricle considering literature data and own experience. MATERIAL AND METHODS: There were 12 patients (6 men and 6 women) with chordoid glioma between 2004 and 2023 (10 patients with lesion of the third ventricle, 1 - lateral ventricle, 1 - pineal region). Only patients with tumors of the third ventricle were analyzed. RESULTS: Total and subtotal resection was performed in 1 and 3 cases, respectively. Five patients underwent partial resection, 1 patient underwent biopsy. The follow-up data were available in 7 out of 10 patients (mean 25 months). Radiotherapy was performed in 4 patients (continued tumor growth in 2 cases). One patient died. CONCLUSION: Chordoid glioma is a benign tumor predominantly localized in the third ventricle. Preoperative MRI and CT in some cases make it possible to suspect chordoid glioma and differentiate this tumor from craniopharyngioma, meningioma and pituitary adenoma by such signs as isointense signal in T1WI, hyper- or isointense signal in T2WI, homogeneous contrast enhancement and edema of basal ganglia in T2 FLAIR images. The only effective treatment for chordoid glioma is surgery. Total resection is often impossible or extremely dangerous due to location of tumor, large size and invasion of the third ventricle. Postoperative mental disorders and diabetes insipidus, including severe hypernatremia, are common that requires mandatory monitoring of water and electrolyte balance.

[Novel BRAF::EPB41L2 gene fusion in posterior fossa pilocytic astrocytoma. Brief communication]. / Novyi tip sliyaniya genov BRAF::EPB41L2 v piloidnoi astrotsitome zadnei cherepnoi yamki. Kratkoe soobshchenie.

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.

[Sarcomas of the central nervous systems. Clinical observations]. / Sarkomy tsentral'noi nervnoi sistemy. Klinicheskie nablyudeniya.

Here we report three patients with rare primary intracranial sarcomas, two of them were CIC-sarcomas and one was a DICER1-sarcoma. Tumors were examined using DNA methylation. It is important to study of CIC fusions and DICER1 mutations in malignant brain tumors.

[Intraosseous metastasis of K27-mutant glioma]. / Vnutrikostnoe metastazirovanie K27-mutantnoi gliomy.

Glioma metastasis outside the central nervous system is a quite rare phenomenon. The disease in a young woman manifested itself as back pain and loss of vision in the left eye. Magnetic resonance imaging (MRI) revealed a tumor of the optic nerve; positron emission tomography showed multiple secondary bone changes. At the same time, MRI detected no signs of neoplasm in the midline brain structures (the brain stem and subcortical nuclei) and spinal cord. Two biopsies (superior iliac spine trephine biopsy and optic nerve tumor biopsy) were performed. There were similar histological tumors; the optic nerve tumor was found to have K27M mutation in the H3F3A gene, whereas the metastatic tumor lacked this mutation (possibly due to the quality and quantity of DNA isolated from the tumor cells). The interesting features of this case are the simultaneous detection of primary and metastatic tumors before receiving any treatment and the absence of the K27M mutation in the H3F3A gene in the metastasis.

[Correct use of Kreatech DNA probes to detect MYC gene amplification in medulloblastomas by fluorescence in situ hybridization]. / Korrektnoe ispol'zovanie DNK-zondov Kreatech dlia vyiavleniia amplifikatsii gena MYC v medulloblastomakh metodom fliuorestsentnoi gibridizatsii in situ.

In most cases, oncogene amplification are prognostic and predictive markers for various tumors, therefore DNA probes are unable to reveal changes in the copy numbers should not be used to diagnose malignant tumors. OBJECTIVE: To comparatively analyze DNA probes from different manufacturers to detect MYC gene amplification in routine practice. MATERIAL AND METHODS: The study material was formalin-fixed paraffin-embedded medulloblastoma fragments from 4 patients, with discrepancies in the results in the detection of MYC gene amplification. RESULTS: MYC gene amplification was determined using DNA probes: Kreatech MYC (8q24)/SE 8, Vysis LSI MYC SO, Vysis CEP 8 (D8Z2) SG, and Zytolight SPEC MYC/CEN 8 Dual Color Probe. The use of the probes Kreatech TERC (3q26)/MYC (8q24)/SE7 Triple-Color probe failed to detect MYC gene amplification; this probe showed a balanced profile of chromosome 8. CONCLUSION: In routine practice, fluorescence in situ hybridization with the DNA probes Kreatech MYC (8q24)/SE 8, Vysis LSI MYC SO, Vysis CEP 8 (D8Z2) SG and Zytolight SPEC MYC/CEN 8 Dual Color Probe can be the method of choice for studying the copy number of the MYC gene. However, the authors strongly recommend that the Kreatech TERC (3q26)/MYC (8q24)/SE7 Triple-Color should not be used for this purpose. In addition, probes for fluorescence in situ hybridization must be necessarily tested in large reference laboratories dealing with one or another area of oncopathology.

[The spectrum of genetic alterations in anaplastic gliomas: and anaplastic oligodendrogliomas]. / Spektr geneticheskikh narushenii v anaplasticheskikh astrotsitomakh i anaplasticheskikh oligodendrogliomakh.

The work explores the molecular genetic features of anaplastic astrocytomas and oligodendrogliomas in a series of 43 cases. The mutational status was studied using domestic chemicals and reagent kits. We revealed clear genetic differences between astrocytic and oligodendroglial tumors and proposed an algorithm to study diagnostic and prognostic markers.

[Antimutagenic systems based on chitosan conjugates with plant antioxidants].

It was shown using various methods that the radical scavenging and radical scavenging activities of chitosan conjugates with phenolic antioxidants of plant origin significantly exceed the corresponding values of their low molecular weight analogs (gallic and syringic acids, quercetin and dihydroquercetin). Cytogenetic analysis of human peripheral blood lymphocytes demonstrated that the conjugates showed pronounced antimutagenic efficiency when the cells were γ-irradiated in vitro at a dose of 2 Gy.

Genetic disorders in primary brain glioblastomas.

Glioblastomas are characterized by a variety of genetic and epigenetic disorders, identification of which allows constantly expanding a list of genes directly involved in carcinogenesis, thus increasing molecular diagnostics, monitoring and predicting disease. Molecular-genetic studies of patients with glioblastomas allowed revealing changes relevant to this disease and determining their prognostic significance. In the future molecular-biological markers along with clinical and therapeutic factors may play a role of separate and independent factors of prognosis in patients with malignant brain lesions.

[Comparative analysis of cytogenetic examination of control groups of subjects carried out in different Russian laboratories].

The incidence of unstable chromosome aberrations in peripheral blood lymphocytes from unirradiated control subjects was analyzed using cytogenetic data obtained from 9 cytogenetic laboratories located in Moscow, St.-Petersburg, Obninsk, and Dubna (Russia). The objective of this study was to estimate the level and spectrum of spontaneous chromosome aberrations in human lymphocytes. 1140 blood samples were taken from 1112 subjects (594 men and 546 women) aged 1 to 72. The total metaphase number was 466795. The uniform Giemsa method for peripheral blood lymphocyte cultures was used. After counting 466795 metaphases, 4288 chromosomal aberrations of various types were classified. The most frequent types of aberrations were acentrics and chromatid deletions. They made up 90% of the total number of aberrations. The remaining 10% were exchange aberrations. The number of chromosome exchanges (dicentrics and centric rings) was twice the number of chromatid exchanges. Overall, the portion ofcells with chromosomal or (and) chromatid aberrations was 0.89 +/- 0.01%; the frequency of acentrics was 0.29 +/- 0.01; the frequency of dicentrics was 0.046 +/- 0.003; the frequency of unstable chromosome aberrations was 0.35 +/- 0.01; and the frequency of chromatid aberrations was 0.57 +/- 0.01 per 100 cells.

[Dynamics of chromosomal aberrations in primates subject to continuous and fractionated gamma-irradiation by equally effective residual doses].

The paper deals with a comparative study of two regimens of Macaca mulatta continuous 2-week gamma- and double fractionated acute irradiation by the total absorbed doses of 250 and 132 cGy, respectively; data about chromosomal aberration rates in peripheral lymphocytes were correlated. Based on calculations it was hypothesized that, regardless of regimen, by day-12 of irradiation the effective residual dose would be same, i.e. approximately 100 cGy. Analysis of instable aberration chromosomes showed similarity of the effect of gamma-irradiation by 137Cs at earlier time points (on days 2-21). In primates with the gamma-irradiation profile close to chronic (Gamma 25) the total rate of chromosomal aberrations and rate of radiation markers remain high, whereas animals exposed to fractionated radiation (Gamma 66) displayed a statistically significant (p < 0.05) reduction in cytogenetic parameters on days 36, 50 and 85. Cytogenetic analysis of peripheral lymphocytes permits the conclusion that though markedly different in dose values and rates, both regimens produce an essentially equal early damaging effect.

[The role of cytogenetic examination for prognosis of remote consequences of irradiation].

Correlation between the level of somatic pathology and cytogenetic characteristics of blood was analyzed in a group of liquidators of the accident at the Chernobyl Nuclear Power Plant (ChNPP). A statistically significant correlation was found between the occurrence of cardiovascular diseases and the level of chromosome aberrations (total frequency of chromosome aberrations, frequency of dicentrics and centric rings, frequency of chromatid aberrations). The results obtained are of great importance for the substantiated prediction of the development of postradiation pathologies.

[Assessment of relative biological effectiveness of tritium using chromosome aberration frequency in human blood lymphocytes].

The aim of this work is to determine Relative Biological Effectiveness (RBE) of tritium beta-irradiation using chromosome aberration frequency in peripheral blood lymphocytes after radiation exposure in vitro and in vivo. The results of the experimental estimation of tritium beta-irradiation RBE in comparison with 60Co gamma-irradiation using analysis of unstable chromosome aberration frequencies in peripheral blood lymphocytes in reference to concrete conditions of the investigation were presented. It was demonstrated that tritium beta-irradiation is in total more effective than gamma-irradiation up to 1 Gy. RBE of tritium beta-irradiation was determined as 2.2 at minimum doses and decreased at higher doses (1 Gy) up to 1.25. For the first time results of the comparative analysis of frequencies of stable chromosome aberrations in two groups of professional nuclear workers (town Sarov) exposed to chronic tritium beta- and gamma-irradiation in remote period were presented. The grater RBE of tritium beta-irradiation was demonstrated. It has been estimated as 2.5.

[Cytogenetic analysis of cosmonaut's blood lymphocytes exposed to low space radiation doses and its place in clinical-physiological health monitoring].

The article discusses the informative significance and pertinence of cytogenetic analysis of peripheral blood lymphocytes to the clinical-physiological investigations of cosmonauts conducted before and after space missions (SM) of varying duration. The authors point out high sensitivity of the technique, relative simplicity and affordability of the analysis of instable chromosomal aberrations including such radiation effect markers as dicentrics and centric rings. Cytogenetic investigation of cosmonauts could be used to estimate ionizing radiation dose, and to predict delayed effects.

[The multiabberant cells in groups of people exposed to radiation due to different situations and their possible biological part].

The results of the analysis of multiaberrant cells (MAC) obtained in the course of long-term investigation of cytogenetic effects in human peripheral blood lymphocytes are presented. MAC were discovered in different groups of the population exposed to the radiation factor. No such cells were found in the control groups. The greatest number of MAC "carriers" was registered among employees of radiochemical plants who had contacts with plutonium salts. The highest frequency of MAC (2.49 +/- 0.59 per 1000 cells) was also revealed in the same group. It exceeded by an order of magnitude the analogous values in other examined groups. In the groups of radiochemical workers, cosmonauts, and miners from Tselinograd the frequency of dicentrics and centric rings was also the highest as compared to that in other groups. The character of chromosome aberrations observed in MAC suggests that they are formed under the action of the radiation factor, and their frequency among different groups of people exposed to radiation makes it possible to assume that the formation of MAC is a result of the action on lymphocytes of alpha-particles emitted by radionuclides incorporated in the organism. Classical MAC was observed in routine studies (FPG staining) are only an extreme manifestation of cell damage. To elucidate the true picture of chromosome rearrangements induced by radiation and the role of MAC in the tumor process, it is necessary to use methodical potentialities of modern molecular cytogenetics, including the FISH method.

[Cytogenetic examination of nuclear specialists exposed to chronic beta-radiation of tritium].

For the first time the cytogenetic examination of the group of nuclear specialists (79 persons) chronically exposed to tritium beta-radiation for a long period was carried out. The frequencies of unstable (conventional method) and stable (FISH-method) chromosome aberrations have been analyzed. 50 years after the beginning of working under the conditions of the increased radiation level the differences (in comparison with control values) were revealed for all cytogenetic parameters. The frequency of the radiation-specific markers (dicentrics and centric rings) exceeds more than 2-fold the control level. A significant but poor correlation between the frequency of unstable aberrations and the total absorbed dose (during the whole working period) was revealed. A retrospective estimation of irradiation doses for 14 nuclear workers was made by the frequency of stable chromosome aberrations. The obtained dose values ranged from 110 to 1250 mSv.

[The analysis of mutations at mini- and microsatellite DNA loci in the family members of a group of occupationally exposed to tritium and tritium oxide plant workers].

Mini/microsatellite (MNS/MCS) loci are efficient tools in solving basic and applied problems in different spheres of biology and medicine due to their unique characteristics - a high frequency of tandem repeats in combination with their wide variability. Specifically, they have been found use as potential markers of genetic effects of ionizing radiation on animals and on human. However there is no general agreement as to the influence of irradiation on the frequency of mutations in hypervariable repetitive DNA sequences up to now. The present work is the study of the mutation frequency at MCS/MNS loci in 19 families of workers occupationally exposed to chronic beta-radiation from tritium and tritium oxide (examined group), and in the control group included 23 families. The results have indicated that the average frequency of microsatellite mutations in the examined group made up 4.7% and exceeds about 7-fold the same parameter of the control group (0.7%). This differences is statistically significant (p = 0.004). The average frequency of minisatellite mutation in the examined group made up 3% while in the control group it was 2 time lower (1.5%), but this difference is not statistically significant. Mutations for 4 MCS and 2 MNS loci were revealed in two children from one family (the total reconstructed dose in their father was about 1000 mSv). If we exclude this family from statistical analysis the frequencies of MCS and MNS mutations in the children of nuclear workers do not statistically differ from the control values.

[Cytogenetic effects on blood lymphocytes of cosmonauts after low doses of space radiation].

Cytogenetic changes in cultures of blood lymphocytes from 37 cosmonauts returned from space flights of varying duration were analyzed. Prolonged stay in space was shown to increase numbers of stable and unstable chromosomal aberrations. Frequency of dicentric and centric rings depends on flight duration, as well as values of accumulated dose from and dose rate of space radiation. Egress into open space leads to an additional growth in the number of chromosomal aberrations. It was found that frequency of chromosomal aberrations in blood lymphocytes remains altered even after several years of cosmonaut's return from space flight. Based on the counts of symmetric translocations obtained with the FISH-technique, mean dose from space radiation following the maiden prolonged space flight amounted to 110 mGy which is in agreement with the biodosimetric data about frequency of dicentric and centric rings (140 mGy).

[The significance of cytogenetic investigation for the estimation of Chernobyl accident consequences].

The results of the cytogenetic investigation of people, which were exposed to radiation in the result of the Chernobyl NPP accident, were presented. Also the possibilities of the application of cytogenetic findings for dose estimations and for the prediction of the radiation influence consequences were examined. During the period of time since 1986 till 2004 the cytogenetic investigations of 1724 liquidators participating in the liquidation works after the Chernobyl accident were carried out. The radiation dose estimated by the frequency of dicentrics in 1986 was about 0.16 Gy. The doses for liquidators were determined by the frequency of translocations (FISH method) during the period from 1992 till 1995. For liquidators who worked in Chernobyl only in 1986 the average dose of radiation was about 0.19 Gy and for liquidators who worked repeatedly during the period from 1986 till 1995 - 0.39 Gy. There was shown that during the whole period of investigation (1986-2004) the frequency of dicentrics in peripheral blood lymphocytes was significantly higher than the control level. The cytogenetic investigation of Bryansk region inhabitants which was carried out in 1992-1994 discovered heightened value in 5 times than the control one. Findings are of great importance for the prediction of ill effects of radiation and for the development of sensitive criterions for early exposure disturbances in state of health.