Hypermethylation Status of NRGN and OLFM1 Promoter Regionsin Glioblastomas Cell Lines

Glioblastomas are the most malignant astrocytic tumors and the most common brain tumors, representing 50 to 60% of allastrocytic tumors. In a previous study, Marie et al (2005) using SAGE and cDNA microarray analyses, followed by real-time PCRvalidation in additional tumor samples, identified potential markers for astrocytomas with distinct levels of malignancy. In thepresent study, we evaluated if the hypoexpression of two of these genes - Neurogranin (NRGN) and Olfactomedin (OLFM1) – isrelated to the hypermethylation of their promoter regions. CpGs islands were identified in the promoter regions of both genesand tumour cell lines (A172 and T98G) were submitted to 5 Aza dC treatment. The treatment was able to induct the expression(1.8 to 8.9 folds) of both genes. Nevertheless, the association between NRGN and OLFM1 hypoexpression and CpG islandhypermethylation could not be established because the CpGs dinucleotides present in the promoter region of these genes wereunmethylated when evaluated by sequencing.

Projeto Genoma Humano e suas implicaçöes para a saúde humana: visäo geral e contribuiçäo brasileira para o projeto / Human Genome Project and its implications to human health: general view and Brazilian contribution to the project

A informaçäo derivada do Projeto Genoma Humano, um esforço internacional para elucidar e caracterizar a seqüência completa de 3X109 pares de bases do genoma humano, vai revolucionar a prática da medicina no séc. XXI por prover instrumentos para determinar o componente genético de virtualmente todas as doenças. As conseqüências para a prática da medicina deveräo ser profundas, tais como a geraçäo de medidas que possam prever o risco, permitir o diagnóstico precoce e promover estratégias de tratamento mais efetivas. Discutem-se as aplicaçöes potenciais do conhecimento adquirido com o HGP, bem como a contribuiçäo brasileira a esse projeto