Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage

Cancer Cell. 2006 Mar;9(3):199-207. doi: 10.1016/j.ccr.2006.02.016.


We studied the relationships between genetic and epigenetic alterations in gastrointestinal cancer by integrating DNA copy number changes determined by arbitrarily primed PCR (AP-PCR) with DNA methylation variations estimated by methylation-sensitive amplified fragment length polymorphism (MS-AFLP). We analyzed about 100 different chromosomal regions by AP-PCR and over 150 random CpG loci by MS-AFLP in human colon and gastric carcinomas. DNA hypomethylation and hypermethylation alterations distributed gradually and increased with cancer patient age, in contrast with the age-independent genomic alterations. Increased DNA hypomethylation and hypermethylation correlated with increased genomic damage, but only hypomethylation was highly significant in multivariate analyses. We conclude that age-dependent accumulation of DNA demethylation precedes diploidy loss in a significant subset of gastrointestinal cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Age Factors
  • DNA Fingerprinting
  • DNA Methylation*
  • DNA, Neoplasm / chemistry*
  • Epigenesis, Genetic
  • Gastrointestinal Neoplasms / genetics*
  • Gene Dosage
  • Humans
  • Polymerase Chain Reaction


  • DNA, Neoplasm