Fang Wei-Jia, Zheng Yi, Wu Li-Ming, Ke Qing-Hong, Shen Hong, Yuan Ying, Zheng Shu-Sen
Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Asian Pac J Cancer Prev. 2012;13(5):1917-21. doi: 10.7314/apjcp.2012.13.5.1917.
Colorectal cancer is one of the leading causes of mortality worldwide. Genome wide analysis studies have identified sequence mutations causing loss-of-function that are associated with disease occurrence and severity. Epigenetic modifications, such DNA methylation, have also been implicated in many cancers but have yet to be examined in the East Asian population of colorectal cancer patients.
Biopsies of tumors and matched non-cancerous tissue types were obtained and genomic DNA was isolated and subjected to the bisulphite conversion method for comparative DNA methylation analysis on the Illumina Infinium HumanMethylation27 BeadChip.
Totals of 258 and 74 genes were found to be hyper- and hypo-methylated as compared to the individual's matched control tissue. Interestingly, three genes that exhibited hypermethylation in their promoter regions, CMTM2, ECRG4, and SH3GL3, were shown to be significantly associated with colorectal cancer in previous studies. Using heatmap cluster analysis, eight hypermethylated and 10 hypomethylated genes were identified as significantly differentially methylated genes in the tumour tissues.
Genome-wide methylation profiling facilitates rapid and simultaneous analysis of cancerous cells which may help to identify methylation markers with high sensitivity and specificity for diagnosis and prognosis. Our results show the promise of the microarray technology in identification of potential methylation biomarkers for colorectal cancers.
结直肠癌是全球主要致死原因之一。全基因组分析研究已鉴定出导致功能丧失的序列突变，这些突变与疾病的发生和严重程度相关。表观遗传修饰，如DNA甲基化，也与许多癌症有关，但尚未在东亚结直肠癌患者群体中进行研究。
获取肿瘤组织活检样本及匹配的非癌组织样本，提取基因组DNA，并采用亚硫酸氢盐转化法，在Illumina Infinium HumanMethylation27 BeadChip芯片上进行比较DNA甲基化分析。
与个体匹配的对照组织相比，分别发现258个和74个基因发生高甲基化和低甲基化。有趣的是，先前的研究表明，在其启动子区域表现出高甲基化的三个基因，即CMTM2、ECRG4和SH3GL3，与结直肠癌显著相关。通过热图聚类分析，在肿瘤组织中鉴定出8个高甲基化基因和10个低甲基化基因作为显著差异甲基化基因。
全基因组甲基化分析有助于对癌细胞进行快速、同步分析，这可能有助于识别具有高灵敏度和特异性的甲基化标志物，用于诊断和预后评估。我们的结果显示了微阵列技术在识别结直肠癌潜在甲基化生物标志物方面的前景。
