title: Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage.
abstract: 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.
authors.affiliation: Burnham Institute for Medical Research, Cancer Genetics and Epigenetics Research Program, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Ikuko
authors.initials: I
authors.lastname: Suzuki
authors.forename: Andreas
authors.initials: A
authors.lastname: Leodolter
authors.forename: Sergio
authors.initials: S
authors.lastname: Alonso
authors.forename: Shina
authors.initials: S
authors.lastname: Horiuchi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamashita
authors.forename: Manuel
authors.initials: M
authors.lastname: Perucho
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000367:Age Factors; D016172:DNA Fingerprinting; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry*; D044127:Epigenesis, Genetic; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm