title: Hypomethylation and hypermethylation of DNA in Wilms tumors.
abstract: We quantitatively analysed hypermethylation at CpG islands in 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, approximately 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.
authors.affiliation: Tulane Cancer Center and Human Genetics Program, Tulane Medical School, New Orleans, Louisiana, LA 70112, USA. ehrlich@tulane.edu
authors.forename: Melanie
authors.initials: M
authors.lastname: Ehrlich
authors.forename: Guanchao
authors.initials: G
authors.lastname: Jiang
authors.forename: Emerich
authors.initials: E
authors.lastname: Fiala
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Dome
authors.forename: Mimi C
authors.initials: MC
authors.lastname: Yu
authors.forename: Tiffany I
authors.initials: TI
authors.lastname: Long
authors.forename: Byungwoo
authors.initials: B
authors.lastname: Youn
authors.forename: Ock-Soon
authors.initials: OS
authors.lastname: Sohn
authors.forename: Martin
authors.initials: M
authors.lastname: Widschwendter
authors.forename: Gail E
authors.initials: GE
authors.lastname: Tomlinson
authors.forename: Murali
authors.initials: M
authors.lastname: Chintagumpala
authors.forename: Martin
authors.initials: M
authors.lastname: Champagne
authors.forename: David
authors.initials: D
authors.lastname: Parham
authors.forename: Gangning
authors.initials: G
authors.lastname: Liang
authors.forename: Karim
authors.initials: K
authors.lastname: Malik
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
mesh_terms: D018899:CpG Islands; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins; D009396:Wilms Tumor / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C411762:RASSF1 protein, human; C000619380:DNMT1 protein, human