Análise de alterações moleculares dos genes TP53, PTEN, IDH1 E IDH2 em amostras de gliomas.

Abstract

Glioma is the term used to describe tumors derived from glial cells. They are divided into subgroups based on the histological morphology and similarity of their cells with differentiated glial cells. Thus, they are classified according to the World Health Organization, into: astrocytomas, oligodendrogliomas, ependymomas and oligoastrocitomas. Like most cancers, gliomas develop as a result of genetic changes that accumulate with tumor progression. Given the importance of mutations in TP53, PTEN, IDH1 and IDH2 genes in different proposals of the genesis and progression of gliomas, the aim of the present study was to analyze the occurrence of mutations in these genes by PCR/SSCP followed by sequencing, comparing the results obtained from tumors of different malignancy grades and evaluating the presence of statistical associations between different variables. The TP53 mutation was found in 12.2% (6/49) of the samples, mostly in the exons 5 and 7. There was no statistical association between the presence of mutations in these genes and the sex, age or tumor grade variables. However, all mutations occurred in astrocytomas, suggesting a role in the genesis and progression of this tumor subtype. Mutations in IDH1 gene were observed in 17.6 % (6 /34) of cases, whereas no mutations in IDH2 gene were identified. Statistical tests showed no significant relationship between the identified mutations in IDH1 and the variables. Regarding PTEN, only a mutation in exon 4 was identified. Considering the grading of tumor with mutations, it was concluded that mutations in IDH1 and TP53 genes are early events in the progression of gliomas, which can be useful in a clinical standpoint as regards the monitoring of patients and development of more specific therapeutic strategies.