Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage.
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.
Suzuki
Koichi
K
Burnham Institute for Medical Research, Cancer Genetics and Epigenetics Research Program, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
Suzuki
Ikuko
I
Leodolter
Andreas
A
Alonso
Sergio
S
Horiuchi
Shina
S
Yamashita
Kentaro
K
Perucho
Manuel
M
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
D004273:DNA, Neoplasm