Tmic-20. stem-cell phenotype with dna hypomethylation is induced by hypoxia in glioblastoma

We examined the correlation between the methylation status of stem cell-related genes and the treatment outcomes in patients with glioblastoma (GBM) with special reference to the pseudopalisading necrosis. Tumor cells around necrotic areas in human GBM tissues highly express the most important EMT inducer, transforming growth factor-β (TGF-β), concurrently with the EMT-related transcriptional factor, TWIST. In addition, the stem cell markers CD133 and alkaline phosphatase (ALPL) were also highly expressed around necrotic foci in GBM tissues. The high expression of TGF-β around necrotic regions was significantly correlated with shorter progression-free survival and overall survival in patients with GBM. High expression of stem cell markers, ALPL, CD133, and CD44 was also correlated with poor outcomes. The genome-wide DNA methylation status was determined using HumanMethylation450 BeadChips, and the methylation status was compared between groups of patients with high expression of TGF-β around necrosis and hypoxia inducible factor-1α(HIF-1α). The genomic DNAs in GBMs with high expression of TGF-β around necrosis and high HIF-1α were more hypomethylated than in other GBMs. Stem cell-related genes including ALPL and CD133 were also significantly hypomethylated in GBMs with high high expression of TGF-β around necrosis. Accumulation of stem cell properties due to aberrant DNA hypomethylation caused by hypoxia is associated with the r...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MICROENVIRONMENT Source Type: research