Epigenetic Inactivation of Tumor Suppressor Genes in Human Cancer

Strategic Insights -

Researchers in the United States have reported a new study on the role of DNA methyltransferases in the epigenetic inactivation of tumor suppressor genes in human cancer. The study, published in the journal Oncogene, used a combination of whole-genome microarray and promoter array analysis to identify genes with altered expression after RNAi-induced suppression of DNMT in a glioblastoma multiforme cell line. The results showed that DNMT1 and DNMT3b knockdown resulted in the restored expression of 308 genes that also contained promoter region hypermethylation.

Key Takeaways:

  • The study identified 308 genes that had restored expression after DNMT1 and DNMT3b knockdown in a glioblastoma multiforme cell line, which also contained promoter region hypermethylation.
  • Of these, 43 genes were also found to be downregulated in glioblastoma tissue samples.
  • The study found that restoration of gene expression was not associated with changes in promoter region methylation, but rather with changes in histone methylation and chromatin conformation.
  • Two of the identified genes exhibited growth suppressive activity in in vitro assays.
  • The researchers concluded that combining targeted genetic manipulations with comprehensive genomic and expression analyses provides a potentially powerful new approach for identifying epigenetically regulated genes in glioblastoma.

Statistics:

  • 308 genes were identified as having restored expression after DNMT1 and DNMT3b knockdown in a glioblastoma multiforme cell line.
  • 43 genes were found to be downregulated in glioblastoma tissue samples.
  • 2 genes exhibited growth suppressive activity in in vitro assays.

Sources:

  • Foltz, G. et al. "DNA methyltransferase-mediated transcriptional silencing in malignant glioma: a combined whole-genome microarray and promoter array analysis." Oncogene, 2009;28(29):2667-77.
  • Cancer Genetics
  • Nature Publishing Group. Publisher contact information for the journal Oncogene.
  • Cancer Weekly editors.