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

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.

我们通过整合任意引物PCR（AP-PCR）测定的DNA拷贝数变化和甲基化敏感性扩增片段长度多态性（MS-AFLP）估计的DNA甲基化变异，研究了胃肠道癌中遗传和表观遗传改变之间的关系。我们用AP-PCR和MS-AFLP分别分析了人结肠癌和胃癌中100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呈逐渐分布，并随年龄增长而增加，与年龄无关的基因组改变相反。DNA低甲基化和高甲基化的增加与基因组损伤的增加相关，但只有低甲基化在多变量分析中具有高度显著性。我们的结论是，在胃肠道肿瘤的一个重要子集中，DNA去甲基化的年龄依赖性积累先于二倍体丢失。

项目成果

Global DNA methylation in gastrointestinal cancer is age dependent and precedes genomic damage

胃肠癌中的整体 DNA 甲基化具有年龄依赖性，并且先于基因组损伤

• 发表时间: 2006
• 期刊: Cancer cell. Mar;9(3)
• 作者: Suzuki K;Suzuzki I;Leodolter A;Alonso S;Horiuchi S;Yamashita K;Perucho M
• 通讯作者: Perucho M