Author(s): Pess?a, Igor Andrade ; Amorim, Carolina Koury ; Ferreira, Wallax Augusto Silva ; Sagica, Fernanda ; Brito, Jos? Reginaldo ; Othman, Moneeb ; Meyer, Britta ; Liehr, Thomas ; Oliveira, Edivaldo Herculano Correa de
Date: 2019
Origin: Oasisbr
Subject(s): Glioma / gen?tica; Sistema Nervoso Central; Genes p53 / gen?tica; S?ndrome do Hamartoma M?ltiplo / gen?tica; Polimorfismo Conformacional de Fita Simples / gen?tica; Hibridiza??o in Situ Fluorescente / gen?tica; Hibridiza??o Gen?tica
This research was funded partially by Funda??o de Amparo ? Pesquisa do Estado do Par? (FAPESPA, Bel?m, PA) (ICAAF 075/2014).
Universidade Federal do Par?. Programa de P?s-gradua??o em Gen?tica e Biologia Molecular. Bel?m, PA, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura de Tecidos e Citogen?tica. Ananindeua, PA, Brasil / Jena University Hospital. Institute of Human Genetics. Jena, Germany.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura de Tecidos e Citogen?tica. Ananindeua, PA, Brasil.
Universidade Federal do Par?. Programa de P?s-gradua??o em Neuroci?ncias e Biologia Celular. Bel?m, PA, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura de Tecidos e Citogen?tica. Ananindeua, PA, Brasil
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura de Tecidos e Citogen?tica. Ananindeua, PA, Brasil
Universidade Federal do Par?. Programa de P?s-gradua??o em Oncologia e Ci?ncias M?dicas. Bel?m, PA, Brazil.
Jena University Hospital. Institute of Human Genetics. Jena, Germany.
Zyto Vision GmbH. Bremerhaven, Germany.
Jena University Hospital. Institute of Human Genetics. Jena, Germany.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura de Tecidos e Citogen?tica. Ananindeua, PA, Brasil / Universidade Federal do Par?. Faculdade de Ci?ncias Naturais. Instituto de Ci?ncias Exatas e Naturais. Bel?m, PA, Brazil.
Abstract: Gliomas are the most frequent primary tumors of central nervous system and represent a heterogeneous group of tumors that originates from the glial cells. TP53, PTEN, and CDKN2A are important tumor suppressor genes that encode proteins involved in sustaining cellular homeostasis by different signaling pathways. Though genetic alterations in these genes play a significant role in tumorigenesis, few studies are available regarding the incidence and relation of concomitant TP53, PTEN, and CDKN2A alterations in gliomas. The purpose of this study was to evaluate the occurrence of mutation and deletion in these genes, through single-strand conformational polymorphism, array-comparative genomic hybridization, and fluorescence in situ hybridization techniques, in 69 gliomas samples. Molecular results demonstrated a significant higher prevalence of TP53, PTEN, and CDKN2A alterations in astrocytoma than other tumor subtypes, and heterozygous deletion was the most frequent event. In addition, a significant association was observed between TP53 and CDKN2A alterations (p = 0.0424), which tend to coexist in low grade astrocytomas (5/46 cases (10.9%)), suggesting that they are early events in development of these tumors, and PTEN and CDKN2A deletions (p = 0.0022), which occurred concomitantly in 9/50 (18%) patients, with CDKN2A changes preceding PTEN deletions, present preferably in high-grade gliomas.
