MUTATIONS OF GENES BRCA1 AND BRCA2 IN WOMEN WITH OVARIAN CANCER EXPOSED TO FACTORS OF CHORNOBYL NUCLEAR ACCIDENT. / MUTATsIÏ U GENAKh BRCA1 TA BRCA2 U ZhINOK, KhVORYKh NA RAK IaIeChNYKIV, IaKI ZAZNALY VPLYVU ChYNNYKIV ChORNOBYL'S'KOÏ KATASTROFY.

OBJECTIVE: to determine a frequency of germline mutations 185delAG, 5382insC in BRCA1 gene and 6174delT in BRCA2 gene in Ukrainian patients with OC including women who were exposed to the factors of Chornobyl nuclear accident. MATERIAL AND METHODS: In the study we enrolled 306 OC patients of different age who were tested for the presence of the major BRCA1 and BRCA2 gene mutations using allele specific multiplex polymerase chain reaction. RESULTS: The mutation frequency in patients exposed to IR with OC (main group) was 5.3 % (2 from 38). Among unexposed patients (control group) 11,2 % (30 from 268) of cases with mutation were identified. However, the dif- ference between the groups was not significant (p = 0.39). It was shown that the BRCA1/2 mutations frequency in the patient of both groups was 10,4 % (32 from 306). The mutation BRCA1 5382insC was positive in 87.5 % (28 from 32) of cases, nevertheless nobody was identified with the allelic variant BRCA2 6174delT among both groups. There was a tendency toward an earlier age of the OC manifestation in the patients exposed to IR due to Chornobyl nuclear accident compared to BRCA-positive women of the control group (р = 0.06). When comparing BRCA-positive and BRCA-negative patients with OC of the main group, there was a statistical significance regarding the earlier age of the disease manifestation in the patients with mutations (р = 0.04). However, such difference was not observed in the control group (р = 0.22). CONCLUSIONS: The frequency of the mutations in exposed to IR and unexposed patients with OC does not differ and depends on a spectrum of studied BRCA1/2 gene mutations, level of DNA amplification and sample number. The allel- ic variant BRCA1 5382insC is dominant and accounts for 87.5 % of the total number of the found mutations. Due to the radiation factor the OC in the BRCA1-positive individuals is realized at the earlier age than in patients negative for these mutations. The incidence of OC after the Chornobyl accident was observed 27-38 years later in a cohort of women who were from 4 to 40 years old at the moment of the nuclear explosion.

Copy number alterations and copy-neutral loss of heterozygosity in Ukrainian patients with primary myelofibrosis.

AIM: To examine frequencies and spectrum of genomic alterations in Ukrainian patients diagnosed with primary myelofibrosis (PMF). MATERIALS AND METHODS: We enrolled 30 Ukrainian patients diagnosed with PMF who were previously tested for usual mutations in mye-loproliferative neoplasms driver genes (JAK2, MPL and CALR). Genomic DNA samples were obtained from peripheral blood leukocytes of these patients. Copy number alterations and copy-neutral loss of heterozygosity (cnLOH) were assessed using a high-density CytoScan HD microarray platform. Statistical significance was evaluated by the Fisher exact test. RESULTS: We identified frequent genomic alterations, but no significant difference in the rates of copy-number loss, copy-number gain, cnLOH, or multiple genomic alterations were found in the groups of PMF patients that were positive for one of the usual mutations in driver genes or negative for such mutations (33.3% and 55.6%, p = 0.4181, 19.0% and 11.1%, p = 1.0000, 61.9% and 44.4%, p = 0.4434, 33.3% and 55.6%, p = 0.4181, respectively). The most frequent alterations were cnLOH at 1p36-1p22, 9p24.3-9p13.3 and 11q12.3-11q25; copy number loss at 7q21-7q36.3 and 13q12.3-13q14.3. Copy number alterations and cnLOH commonly affected the EZH2, LAMB4, CBL, CUX1, ATM, RB1 and TP53 genes, in addition to JAK2, MPL and CALR. CONCLUSION: We demonstrated the spectrum of genomic alterations in the groups of the Ukrainian PMF patients with or without the usual mutations in the specific driver genes. We identified several potential genes, which may be involved in the myeloproliferative neoplasms development and their phenotype modification (EZH2, LAMB4, CBL, CUX1, ATM, RB1 and TP53).

EVALUATION OF BURDENSOME SYMPTOMS IN PATIENTS WITH RADIATION6ASSOCIATED AND SPONTANEOUS MYELOPROILIFERATIVE NEOPLASMS WITH THE USE OF OPTIMIZED SELF-ASSESSMENT MPN-SAF TSS. / OTsINKA OBTIaZhLYVYKh SYMPTOMIV U KhVORYKh NA RADIATsIINO-ASOTsIIOVANI TA SPONTANNI MIIeLOPROLIFERATYVNI NEOPLAZIÏ Z VYKORYSTANNIaM ADAPTOVANOÏ ShKALY SAMOOTsINKY MPN-SAF TSS.

OBJECTIVE: To investigate the intensity of burdensome symptoms using self-assessment MPN-SAF TSS in patientswith radiation-associated and spontaneous myeloproiliferative neoplasms (MPNs). MATERIALS AND METHODS: The study included 89 patients with radiation-associated and spontaneous MPNs, the bur-densome symptoms of MPN were determined using MPN-SAF TSS. RESULTS: The average score for complaints in patients with radiation-associated MPNs was significantly higher thanin patients with spontaneous MPNs - 43.46 and 25.04 points, respectively (p = 0.003). MPN patients classified bysubtypes also showed differences regarding intensity of burdensome MPN symptoms, demonstrating significantlyhigher average score of complaints among primary myelofibrosis patients (35.60), compared to polycythemia vera(29.60) and essential thrombocythemia (18.05) patients, (p = 0.005). Our study did not reveal any influence of theJAK2 V617F mutation on MPN burdensome symptoms intensity in MPN patients. CONCLUSIONS: We demonstrated a higher intensity of the MPN burdensome symptoms determined by the optimizedself-assessment MPN-SAF TSS in patients with radiation-associated, and in primary myelofibrosis patients, indicat-ing increased severity of patient's general conditions at the stage of diagnosis verification. It is advisable to usethe optimized MPN-SAF TSS at the moment of molecular genetic testing during the diagnosis of MPN for selectionor modifying treatment strategies in order to achieve better quality of life for patients.

Reserch of the gene polymorphism TOX3 / LOC643714 and the risk of breast cancer development in persons exposed to ionizing radiation after Chornobyl disaster. / DOSLIDZhENNIa POLIMORFIZMU GENA TOX3/LOC643714 TA RYZYKU VYNYKNENNIa RAKU MOLOChNOÏ ZALOZY U OSIB, IaKI ZAZNALY DIÏ IONIZUIuChOÏ RADIATsIÏ VNASLIDOK AVARIÏ NA ChORNOBYL'S'KIY̆ AES.

OBJECTIVE: The objective of this work was to identify and compare the polymorphism of the rs3803662 polymorphism of the TOX3/LOC643714 gene in breast cancer patients who have undergone ionizing radiation due to the Chornobyl accident and in patients without ionizing radiation (IR) in the history. MATERIALS AND METHODS: The determination of the rs3803662 polymorphism of the TOX3/LOC643714 gene was per formed by polymerase chain reaction (PCR) in 83 patients with breast cancer: 42 subjects who were exposed to ion izing radiation due to the Chornobyl accident, 41 people without ionizing radiation in history and 17 controls in Ukraine without cancer pathology. In order to compare the obtained data on spontaneous and radiation associated breast cancer and to calculate the differences in the frequencies of alleles and the risk of oncopathology, data from literature on control groups of the populations of the Russian Federation, Sweden, and the United Kingdom were used. RESULTS: Comparing with the literature data and the group of exposed subjects, the homozygous carriers of the minor alleles of the TOX3/LOC643714 ТТ gene revealed an increased risk of developing breast cancer: OR = 2.89, p = 0.02 (CI 95% 1.17 7,16). In subjects without the influence of IR in history, the carrier of homozygous minor axis of the gene TOX3/LOC643714 ТТ is also associated with the risk of breast cancer: OR = 3.83, p = 0.0002 (CI 95% 0.82-14.14). In the homozygous carriers of the minor alleles of the TOX3 / LOC643714 gene exposed to IR, there was no increase in the risk of developing breast cancer (OR = 0.65, p = 0.46, CI 95% 0.21-2.04) compared with the con trol group of Ukrainian population. CONCLUSIONS: The carrier of homozygous minor alleles of the TOX3/LOC643714 gene is not a risk factor for the devel opment of breast cancer under conditions of exposure to ionizing radiation in the study group of the Ukrainian population.

Prognosis of probability of BRCA1 and BRCA2 mutations carriage in women with compromised family history of breast and/or ovarian cancer.

UNLABELLED: Burdened family history of breast and/or ovarian cancer may indicate the mutations carriage in the BRCA1 and BRCA2 genes. OBJECTIVE: Estimation and compare of the Manchester Scoring system, Penn II and Myriad algorithm in an ability to distinguish the cases with BRCA1/2 mutation those and no mutant alleles at the individual level among the Ukrainian women with early onset of a breast cancer and/or compromised family history with breast cancer and/or ovarian cancer. MATERIAL AND METHODS: Results of genealogy, molecular genetic and morphological study from 44 females with breast cancer, with early development of the disease or family history of a breast cancer and/or ovarian cancer were the material of research. Determination of carriers BRCA1 and BRCA2 mutations among women was performed by Manchester Scoring system and Penn II and Myriad algorithm. RESULTS AND CONCLUSIONS: Manchester Scoring system has better capacity to distinguish patients with and without mutant alleles at the individual level. The area under the curve of Manchester Scoring system is 0.84, Penn II - 0.66, Myriad - 0.68.