ABSTRACT
Aberrant methylation of CpG islands located in promoter regions represents one of the major mechanisms for silencing cancer-related genes in tumor cells. We determined the frequency of aberrant CpG island methylation for several tumor-associated genes: DAPK, MGMT, p14ARF, p16INK4a, TP73, RB1 and TIMP-3 in 55 brain tumors, consisting of 26 neuroepithelial tumors, 6 peripheral nerve tumors, 13 meningeal tumors and 10 metastatic brain tumors. Aberrant methylation of at least one of the seven genes studied was detected in 83.6 percent of the cases. The frequencies of aberrant methylation were: 40 percent for p14ARF, 38.2 percent for MGMT, 30.9 percent for, p16INK4a, 14.6 percent for TP73 and for TIMP-3, 12.7 percent for DAPK and 1.8 percent for RB1. These data suggest that the hypermethylation observed in the genes p14ARF, MGMT and p16INK4a is a very important event in the formation or progression of brain tumors, since the inactivation of these genes directly interferes with the cell cycle or DNA repair. The altered methylation rate of the other genes has already been reported to be related to tumorigenesis, but the low methylation rate of RB1 found in tumors in our sample is different from that so far reported in the literature, suggesting that perhaps hypermethylation of the promoter is not the main event in the inactivation of this gene. Our results suggest that hypermethylation of the promoter region is a very common event in nervous system tumors.
Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Brain Neoplasms , CpG Islands , Epigenesis, Genetic , Brazil , Chromosome Deletion , Gene Expression , Methylation , Polymerase Chain ReactionABSTRACT
Expone que la neurofibromatosis tipo 2 (NF2) es una enfermedad caracterizada por una predisposición a desarrollar múltiples tumores del sistema nervioso central, especialmente neurinomas y menigiomas. Se ha propuesto que algunos tumores esporádicos y tumores asociados a NF2 pueden ser el producto de la inactivación del gen NF2. Se analizaron 83 meningiomas esporádicos y 26 neurinomas esporádicos para el estudio de mutaciones del NF2 por la técnica de PCR-SSCP (polimorfismo en la conformación de la cadena de la polimerasa), identificando 16 casos alterados en 4 de 6 exones estudiados. Con el fin de aumentar la sensibilidad de la SSCP se modificaron las condiciones de los geles, incrementando de aproximadamente 75xcto a un 90xcto la eficiencia en la detección de mutaciones. Este constituye el primer estudio encaminado a optimar la SSCP para cada exón del gen NF2.