Klin Padiatr 2004; 216 - 54
DOI: 10.1055/s-2004-828599

Genome wide methylation analysis of gliomas by a microarray based technology

A Waha 1, J Felsberg 1, A Waha 1, D Ehrentaut 1, T Hui-Ming Huang 2, PS Yan 2, OD Wiestler 3, T Pietsch 1
  • 1Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany
  • 2Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, OH, USA
  • 3Deutsches Krebsforschungszentrum, Heidelberg, Germany

Changes of DNA methylation play a central role in carcinogenesis. Extensive hypermethylation and consecutive transcriptional silencing of tumorsuppressor genes has been documented in multiple tumor entities. The development of a microarray based technology known as differential methylation hybridization has significantly improved the genome wide search for hypermethylated genes. Based on this protocol we have developed a novel microarray containing 7680 CpG rich fragments of the human genome to investigate epigenetic alterations in cancer. Here we used this technology to identify novel genes de novo methylated in human brain tumors. In a set of 50 gliomas of different histology and malignancy we have identified novel targets for epigenetic silencing. A total of 763 DNA fragments showed methylation in at least one of the tumor samples. The methylation of selected DNA sequences has been confirmed in an expanded set of tumors by methylation specific methylation specific PCR or bisulfite sequencing. In summary we performed the first microarray based methylation study on gliomas and present a set of novel candidate genes affected in these neoplasms.