Hypomethylation and hypermethylation of DNA in Wilms tumors

Melanie Ehrlich, Guanchao Jiang, Emerich Fiala, Jeffrey S. Dome, Mimi C. Yu, Tiffany I. Long, Byungwoo Youn, Ock Soon Sohn, Martin Widschwendter, Gail E. Tomlinson, Murali Chintagumpala, Martin Champagne, David Parham, Gangning Liang, Karim Malik, Peter W. Laird

Research output: Contribution to journalArticle

145 Scopus citations

Abstract

We quantitatively analysed hypermethylation at CpG islands la the 5′ ends of 12 genes and one non-CpG island 5′ region (MTHFR) in 31 Wilms tumors. We also determined their global genomic 5-methylcytosine content. Compared with various normal postnatal tissues, ∼40-90% of these pediatric kidney cancers were hypermethylated in four of the genes, MCJ, RASSF1A, TNFRSF12 and CALCA as determined by a quantitative bisulfite-based assay (MethyLight). Interestingly, the non-CpG island 5′ region of MTHFR was less methylated in most tumors relative to the normal tissues. By chromatographic analysis of DNA digested to deoxynucleosides, about 60% of the Wilms tumors were found to be deficient in their overall levels of DNA methylation. We also analysed expression of the three known functional DNA methyltransferase genes. No relationship was observed between global genomic 5-methylcytosine levels and relative amounts of RNA for DNA methyltransferases DNMT1, DNMT3A, and DNMT3B. Importantly, no association was seen between CpG island hypermethylation and global DNA hypomethylation in these cancers. Therefore, the overall genomic hypomethylation frequently observed in cancers is probably not just a response or a prelude to hypermethylation elsewhere in the genome. This suggests that the DNA hypomethylation contributes independently to oncogenesis or tumor progression.

Original languageEnglish (US)
Pages (from-to)6694-6702
Number of pages9
JournalOncogene
Volume21
Issue number43
DOIs
StatePublished - 2002

Keywords

  • DNA hypermethylation
  • DNA hypomethylation
  • Wilms tumors

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Ehrlich, M., Jiang, G., Fiala, E., Dome, J. S., Yu, M. C., Long, T. I., Youn, B., Sohn, O. S., Widschwendter, M., Tomlinson, G. E., Chintagumpala, M., Champagne, M., Parham, D., Liang, G., Malik, K., & Laird, P. W. (2002). Hypomethylation and hypermethylation of DNA in Wilms tumors. Oncogene, 21(43), 6694-6702. https://doi.org/10.1038/sj.onc.1205890