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

DNA甲基化改变及其与胃肠道癌症基因组不稳定性的关系

• 批准号: 17591387
• 负责人: SUZUKI Koichi
• 金额: $ 2.11万
• 依托单位: Jichi Medical University (2006)Hamamatsu University School of Medicine (2005)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591387/
• 关键词: genetic alteration; epigenetic alteration; methylation; demethylation; aging; gastric cancer; colon cancer; carcinogenesis; 胃がん; 大腸がん; 遺伝子修飾の異常; genetic alteration; epigenetic alteration; methylation; demethylation; aging; gastric cancer; colon cancer; carcinogenesis; 胃がん; 大腸がん; 遺伝子修飾の異常

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.

我们通过整合由任意启动PCR（AP-PCR）与DNA甲基化变化确定的DNA拷贝数变化与通过甲基化敏感的扩增片段长度多态性（MS-AFLP）确定的DNA拷贝数变化（MS-AFLP）来研究胃肠道癌的遗传和表观遗传改变之间的关系。我们通过AP-PCR分析了大约100个不同的染色体区域，在人类结肠和胃癌中，MS-AFLP超过150个随机CPG基因群。与非年龄非依赖性的基因组改变相反，DNA的低甲基化和高甲基化改变逐渐分布并随着癌症患者的年龄而增加。 DNA降量甲基化和高甲基化与基因组损伤的增加相关，但在多元分析中仅降低甲基化非常显着。我们得出的结论是，在胃肠道癌的显着子集中，DNA脱甲基化的年龄依赖性积累在二倍体损失之前。