Abstracts of the 6th Canadian Neuro-Oncology Meeting May 18–21, 1994 Lake Louise, Alberta

Abstract

fibrillary acidic protein (GFAP) is an intermediate filament specifically expressed In gUM cells which conlributes to and malnlains the stability of the astrocyte's cytoskeleton. We have previously observed that GFAP expression is reduced in rnalignant glial tmnors, and that the up-regulation of GFAP expression affects glial cell proliferation and tumorigenicity (Cancer Res. 53:3624, 1993). To determine how the transcription of the GFAP is repressed in malignant glial tumors, we looked for genomle rearrangements of the GFAP gene by Southern analysis, but none was found. However, we have shown for the first time that the GFAP gene was hyper-methylated in five GFAP negative glioma cells. This hyper-methylalion was also detected in other GFAP negative non-glial cells. Both hyper-and hypo-methylation of DNA have been shown in a variety of tumor types to be important [actors affecting gene transcription. This methylation-mediated repression of transcription is thought to be a candidate mechanism for the decreased expression of several tumor suppressor genes, and may also be one mechanism by which there is loss of GFAP gene expression in malignant gliomas (Supported by NCI Canada).