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. © 2006 Elsevier Inc.
Suzuki, K., Suzuki, I., Leodolter, A., Alonso, S., Horiuchi, S., Yamashita, K., & Perucho, M. (2006). Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage. Cancer Cell, 9(3), 199–207. https://doi.org/10.1016/j.ccr.2006.02.016