Epigenetic lesions at the H19 locus in Wilms' tumour patients

Nat Genet. 1994 Jul;7(3):440-7. doi: 10.1038/ng0794-440.

Abstract

To test the potential role of H19 as a tumour suppressor gene we have examined its expression and DNA methylation in Wilms' tumours (WTs). In most WTs (18/25), H19 RNA was reduced at least 20-fold from fetal kidney levels. Of the expression-negative tumours ten retained 11p15.5 heterozygosity: in nine of these, H19 DNA was biallelically hypermethylated and in two cases hypermethylation locally restricted to H19 sequences was also present in the non-neoplastic kidney parenchyma. IGF2 mRNA was expressed in most but not all WTs and expression patterns were consistent with IGF2/H19 enhancer competition without obligate inverse coupling. These observations implicate genetic and epigenetic inactivation of H19 in Wilms' tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • DNA, Neoplasm / chemistry
  • DNA, Neoplasm / genetics*
  • Enhancer Elements, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes*
  • Genes, Tumor Suppressor*
  • Genes, ras
  • Genomic Imprinting
  • Genotype
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Kidney / embryology
  • Kidney / metabolism
  • Kidney Neoplasms / genetics*
  • Male
  • Methylation
  • Oncogenes
  • RNA, Messenger / genetics*
  • RNA, Neoplasm / genetics*
  • Repetitive Sequences, Nucleic Acid
  • Transcription, Genetic
  • Wilms Tumor / genetics*

Substances

  • DNA, Neoplasm
  • RNA, Messenger
  • RNA, Neoplasm
  • Insulin-Like Growth Factor II