title: Expression Analysis of Genes Involved in the RB/E2F Pathway in Astrocytic Tumors.
abstract: Astrocytic gliomas, which are derived from glial cells, are considered the most common primary neoplasias of the central nervous system (CNS) and are histologically classified as low grade (I and II) or high grade (III and IV). Recent studies have shown that astrocytoma formation is the result of the deregulation of several pathways, including the RB/E2F pathway, which is commonly deregulated in various human cancers via genetic or epigenetic mechanisms. On the basis of the assumption that the study of the mechanisms controlling the INK4/ARF locus can help elucidate the molecular pathogenesis of astrocytic tumors, identify diagnostic and prognostic markers, and help select appropriate clinical treatments, the present study aimed to evaluate and compare methylation patterns using bisulfite sequencing PCR and evaluate the gene expression profile using real-time PCR in the genes CDKN2A, CDKN2B, CDC6, Bmi-1, CCND1, and RB1 in astrocytic tumors. Our results indicate that all the evaluated genes are not methylated independent of the tumor grade. However, the real-time PCR results indicate that these genes undergo progressive deregulation as a function of the tumor grade. In addition, the genes CDKN2A, CDKN2B, and RB1 were underexpressed, whereas CDC6, Bmi-1, and CCND1 were overexpressed; the increase in gene expression was significantly associated with decreased patient survival. Therefore, we propose that the evaluation of the expression levels of the genes involved in the RB/E2F pathway can be used in the monitoring of patients with astrocytomas in clinical practice and for the prognostic indication of disease progression.
authors: Francisco Mauro Salzano Molecular Biology Laboratory, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará-UFPA)-Belém, Pará, Brazil.
authors: Wallax Augusto Silva
authors: WA
authors: Ferreira
authors: Francisco Mauro Salzano Molecular Biology Laboratory, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará-UFPA)-Belém, Pará, Brazil.
authors: Mariana Diniz
authors: MD
authors: Araújo
authors: Francisco Mauro Salzano Molecular Biology Laboratory, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará-UFPA)-Belém, Pará, Brazil.
authors: Nilson Praia
authors: NP
authors: Anselmo
authors: Tissue Culture and Cytogenetics Laboratory, Evandro Chagas Institute (Instituto Evandro Chagas)-Belém, Pará, Brazil.
authors: Edivaldo Herculano Correa
authors: EH
authors: de Oliveira
authors: Ophir Loyola Hospital-Belém, Pará, Brazil.
authors: José Reginaldo Nascimento
authors: JR
authors: Brito
authors: Human Cytogenetics Laboratory, Institute of Biological Sciences, UFPA-Belém, Pará, Brazil.
authors: Rommel Rodriguez
authors: RR
authors: Burbano
authors: Francisco Mauro Salzano Molecular Biology Laboratory, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará-UFPA)-Belém, Pará, Brazil.
authors: Maria Lúcia
authors: ML
authors: Harada
authors: Francisco Mauro Salzano Molecular Biology Laboratory, Institute of Biological Sciences, Federal University of Pará (Universidade Federal do Pará-UFPA)-Belém, Pará, Brazil; Agricultural Technology Center, Socio-environmental and Water Management Institute, Federal Rural University of Amazônia (Universidade Federal Rural da Amazônia)-Belém, Pará, Brazil.
authors: Bárbara do Nascimento
authors: Bdo N
authors: Borges
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D050684:E2F Transcription Factors / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D063150:Polycomb Repressive Complex 1 / Q000235:genetics; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult
chemical_list: C069077:BMI1 protein, human; C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050684:E2F Transcription Factors; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D063150:Polycomb Repressive Complex 1