DNA methylation alterations and their relationship to genomic instability in gastrointestinal cancer

我们通过整合任意引物PCR （AP-PCR）测定的DNA拷贝数变化和甲基化敏感扩增片段长度多态性（MS-AFLP）估计的DNA甲基化变化，研究了胃肠道癌症遗传和表观遗传改变之间的关系。我们用AP-PCR和MS-AFLP分析了人类结肠癌和胃癌的100多个不同的染色体区域和150多个随机CpG位点。DNA低甲基化和高甲基化改变随着癌症患者的年龄逐渐分布并增加，与年龄无关的基因组改变相反。增加的DNA低甲基化和高甲基化与增加的基因组损伤相关，但在多变量分析中只有低甲基化是高度显著的。我们的结论是，年龄依赖性的DNA去甲基化积累先于二倍体丧失在胃肠道癌症的一个重要子集。

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.