Inomistova M. Expression of genes involved in the regulation of p53 pathway in neuroblastoma

The thesis is dedicated to the investigation of changes in gene expression, including microRNAs, involved in the regulation of p53 pathway in neuroblastoma to identify new prognostic factors of the disease. Alterations in MDM2, TP53 and GSTP1 mRNA expression of genes in neuroblastoma tumor tissue were studied. Tumors from 358 patients with neuroblastoma, peripheral blood of patients (128 samples) and healthy people (158 samples) were analyzed. Prognostic criteria for neuroblastoma were established that characterize changes in functioning of p53 pathway. High MDM2 expression in neuroblastoma tumor tissue was associated with the risk of relapses and poor disease prognosis. Patients with high levels of TP53 expression and low MDM2 expression were characterized by a favorable prognosis. G313G homozygous variant of GSTP1 gene was associated with a poor prognosis. Disease prognosis of patients with low GSTP1 expression was determined by the gene polymorphic variant. Underexpression of miR-34a, miR-137 and miR-885-5p was associated with adverse clinical and biological characteristics of neuroblastoma and decreased of patients' survival, while miR-380-5p overexpression in patients with MYCN amplification correlated with poor disease prognosis