Genetic and Epigenetic Modifications of Sox2 Contribute to the Invasive Phenotype of Malignant Gliomas

摘要: We undertook this study to understand how the transcription factor Sox2 contributes malignant phenotype of glioblastoma multiforme (GBM), most aggressive primary brain tumor. initially looked for unbalanced genomic rearrangements in locus 42 GBM samples and found that was amplified 11.5% overexpressed all samples. These results prompted us further investigate mechanisms involved overexpression GBM. analyzed methylation status promoter because high CpG density promoters are associated with key developmental genes. The presented a island hypomethylated patient when compared normal cell lines. Treatment Sox2-negative glioma lines 5-azacitidine resulted re-expression change promoter. confirmed these by analyzing data from cases generated Cancer Genome Atlas project. observed (86%; N = 414), gene amplification (8.5%; 492), Sox 2 hypomethylation (100%; 258), suggesting relevance GBMs. To explore role Sox2, we performed vitro analysis tumor stem cells (BTSCs) established Downmodulation BTSCs loss their self-renewal properties. Surprisingly, ectopic expression not sufficient support self-renewal, additional factors required. Furthermore, induce invasion migration cells, knockdown experiments demonstrated essential maintaining Altogether, our underscore importance pleiotropic suggest it could be used as therapeutic target