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Information × Registration Number 0216U001135, 0113U002151 , R & D reports Title Investigate the genetic and epigenetic mechanisms of neuroblastoma progression and determine the factors of the disease prognosis in children popup.stage_title Head Khranovska Natalia, Registration Date 25-01-2016 Organization Ukrainian Research Institute of Oncology and Radiology popup.description2 Research object - biological material of 91 patients with verified diagnosis of neuroblastoma. Research methods - molecular-genetic, cytogenetic, morphologic, biochemical, statistics. Equipment - instruments for real-time PCR 7300/7500 Real-Time PCR Systems, "AppliedBiosystems", USA; fluorescent microscope Imager.M1 "Axio Zeizz", Germany; scales WPS, centrifuge OPN3-UHL. The loss of chromosomal locus 17p, where ТР53 gene is allocated, has been observed only in 2,5 % of neuroblastoma (NB) patients. However, hyperexpression of MDM2 gene - a negative regulator of p53, which led to the dysfunction of p53/MDM2 signaling pathway, has been found in 53 % of NB patients. It has been shown that increase in MDM2 expression level is associated with unfavourable prognosis and lower disease-free survival of NB patients regardless to disease stage and MYCN status. Thus, 3-year disease-free survival of patients with high MDM2 expression level was 12% compared to 66% in group of patients with low MDM2 expression level. 11q23 deletion in tumor cells has been found in 20% of NB patients together with non-amplified MYCN status and in 1 case - with deletion in short arm of 17 chromosome. 11q23 deletion with non-amplified MYCN gene status in NB patients was associated with negative disease outcome. It has been shown that miR-380-5p microRNA expression level as an independent marker have no association with NB disease outcome, meanwhile low expression levels of miR-885-5p, miR-380-5p and miR-137 was associated with unfavourable disease prognosis. Thereby, low expression levels of miR-885-5p, miR-380-5p and miR-137 in NB tumor cells have been observed more often in patients with III-IV compared to I-III disease stages and correlate with amplified MYCN gene status and high MDM2 expression level. Beside that, low miR-137 expression level was found in 73% of NB patients. Absence of retinoic acid receptor gene (RARB2) expression in tumor cells has been found in 21,3% of NB patients. Moreover, RARB2 expression level was significantly higher in tumors with amplified MYCN gene compared to those with normal MYCN status. Thus, functional status of RARB2 gene should be a subject for further investigation. The obtained results indicate that functional defects in p53-MDM2 signalling pathway caused by MDM2 gene hyperexpression or augmented expression of microRNAs miR-885-5p, miR-137 and miR-380-5p are associated with unfavourable NB prognosis. Above-mentioned markers could be recommended as a part of molecularly-genetic component of NB risk stratification system. Product Description popup.authors Іномістова М.В. Горбач О.І. Свергун Н.М. Скачкова О.В. Храновська Н.М. popup.nrat_date 2020-04-02 Close