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Identification and characterization of single-nucleotide polymorphisms in microRNAs involved in glioblastoma susceptibility patients

Grant number: 16/25108-7
Support type:Scholarships in Brazil - Master
Effective date (Start): December 01, 2017
Effective date (End): February 28, 2019
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Manoela Marques Ortega
Grantee:Jéssica Silva dos Santos
Home Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Glioblastoma multiforme (GBM) represents a significant portion of neurological tumors. It is characterized by poorly differentiated neoplastic astrocytes with areas of vascular proliferation and necrosis. The survival rate of the patients is inversely proportional to the degree of the tumor, where grade IV is the most aggressive with a relatively short prognosis. Biological heterogeneity is one of the major obstacles to effective treatment of GBM. The objective of this study is to identify single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) as a risk factor and susceptibility to GBM. To accomplish this goal, an overall analysis of about 278,000 SNPs located in miRNAs regions with 80 DNA samples collected from paraffin-preserved tumor tissues from patients with GBM at diagnosis and 80 DNA samples collected from normal brain tissue of individuals undergoing surgery for removal of brain tumor or trauma, using the Axiom® miRNA Target Site Genotyping Array (Affymetrix). Next, a selection of SNPs in miRNAs relevant in GBM will be performed compared to normal brain tissue sample. After a selection of SNPs in miRNAs candidates as a risk factor for the disease, the influence of the different genotypes (wild homozygote, heterozygous and variant homozygote) will be validated by real-time polymerase chain reaction (qPCR) in another 200 samples of RNA from tumor tissues preserved in paraffin from patients with GBM at diagnosis. Subsequently, a relevant SNP in GBM will be selected to identify the frequency of the genetic variants in DNA samples from GBM patients compared to DNA samples from peripheral blood of 300 healthy subjects by RT-PCR. According to the above, the objective of this study is to identify SNPs in miRNAs and susceptibility to GBM in the Brazilian population.