title: A microarray-based DNA methylation study of glioblastoma multiforme.
abstract: Glioblastoma multiforme (GBM) is the most frequent and devastating primary brain tumor in adults. The presence of epigenetic lesions, like hypermethylation of known tumor suppressor genes such as MGMT, has been widely described in GBM, but to our knowledge, a genome-wide profile of DNA methylation changes in these lethal tumors is not yet available. In the present analysis, we have quantified the DNA methylation level of 1,505 CpG dinucleotides (807 genes) in 87 consecutive GBMs using universal BeadArrays. Supervised cluster analyses identified 25 and seven genes that were respectively hypermethylated and hypomethylated in more than 20% of the cases studied. The most frequently hypermethylated genes were HOXA11, CD81, PRKCDBP, TES, MEST, TNFRSF10A and FZD9, being involved in more than half of the cases. Studying the biological features of hypermethylated genes, we found that the group of genes hypermethylated in GBM was highly enriched (41%, p < 0.001) for targets of the PRC2 (Polycomb repressive complex 2) in embryonic stem cells. This suggests that GBM might be derived from precursor cells with stem cell-like features. DNA methylation profiles were associated with overall survival in GBM, and we confirmed the favorable prognostic impact of MGMT methylation in patients treated with alkylating agents. Furthermore, we identified that promoter hypermethylation of the transcription factor gene GATA6 (occurring in 30% of GBM) was significantly associated with unfavorable patient survival.
authors: Department of Neurosurgery, University of Goettingen, Goettingen WT-084071, Germany. ramon.martinez@med.uni-goettingen.de
authors: Ramon
authors: R
authors: Martinez
authors: Jose I
authors: JI
authors: Martin-Subero
authors: Veit
authors: V
authors: Rohde
authors: Matthias
authors: M
authors: Kirsch
authors: Miguel
authors: M
authors: Alaminos
authors: Agustin F
authors: AF
authors: Fernandez
authors: Santiago
authors: S
authors: Ropero
authors: Gabriele
authors: G
authors: Schackert
authors: Manel
authors: M
authors: Esteller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D063146:Polycomb-Group Proteins; D012097:Repressor Proteins