Demethylation of repetitive DNA sequences in neuroblastoma

Genes Chromosomes Cancer. 1996 Dec;17(4):234-44. doi: 10.1002/(SICI)1098-2264(199612)17:4<234::AID-GCC5>3.0.CO;2-4.


Altered genomic methylcytosine content has been described for a number of tumor types, including neuroblastoma. However, it remains to be determined for different tumor types whether specific loci or chromosomal regions are affected by a methylation change or whether the change is random. We have implemented a computer-based approach for the analysis of two-dimensional separations of human genomic restriction fragments. Through the use of methylation-sensitive restriction enzymes, methylation differences in genomic DNA between tumor and normal tissues can be detected. We report the cloning and sequencing of two fragments detectable in two-dimensional separations of genomic DNA of neuroblastomas. These fragments were found to be a part of repetitive units that exhibited demethylation in neuroblastoma relative to other tumor types. Our finding of a distinct pattern of methylation of repetitive units in neuroblastoma suggests that altered methylation at certain loci may contribute to the biology of this tumor.

MeSH terms

  • Base Sequence
  • Blotting, Southern
  • DNA Methylation*
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • Humans
  • In Situ Hybridization, Fluorescence
  • Molecular Sequence Data
  • Neuroblastoma / genetics*
  • Repetitive Sequences, Nucleic Acid
  • Restriction Mapping
  • Sequence Analysis, DNA*


  • Deoxyribonucleases, Type II Site-Specific
  • GCGGCCGC-specific type II deoxyribonucleases