Tan Sing-Huang, Ida Hiroshi, Goh Boon-Cher, Hsieh Wenson, Loh Marie, Ito Yoshiaki
Department of Hematology-Oncology, National University Hospital, 5 Lower Kent Ridge Road, 119074, Singapore.
Anticancer Res. 2006 Nov-Dec;26(6B):4287-92.
Aberrant methylation of cytosine in promoter CpG islands is a recognized contributory process to carcinogenesis. This study explores the methylation profile of RUNX3 in combination with p16, RASSF1A, CDH1 and hMLH1 in nasopharyngeal carcinoma (NPC) patients.
Genomic DNA was extracted from 19 fresh frozen NPC biopsies, which were then subjected to bisulfite conversion and methylation-specific PCR for analysis of promoter hypermethylation for the five respective genes. Three cell lines, SNU1, RKO and LS174T, were used as controls.
The incidences of promoter methylation were as follows: RUNX3 0/19 (0%), p16 6/19 (32%), RASSF1A 13/19 (68%), CDH1 9/19 (47%) and hMLH1 4/19 (21%). Ninety-five percent of the tumor specimens displayed aberrant methylation in at least one of these genes. No significant correlation between methylation status of these genes and clinical parameters was found.
Methylation of multiple genes is involved in critical pathways for cancer development in NPC. Promoter hypermethylation for RUNX3 was, however, not present.
启动子CpG岛中胞嘧啶的异常甲基化是一种公认的致癌促成过程。本研究探讨鼻咽癌(NPC)患者中RUNX3与p16、RASSF1A、CDH1和hMLH1的甲基化谱。
从19例新鲜冷冻的NPC活检组织中提取基因组DNA,然后进行亚硫酸氢盐转化和甲基化特异性PCR,以分析这五个基因各自启动子的高甲基化情况。使用三种细胞系SNU1、RKO和LS174T作为对照。
启动子甲基化的发生率如下:RUNX3为0/19(0%),p16为6/19(32%),RASSF1A为13/19(68%),CDH1为9/19(47%),hMLH1为4/19(21%)。95%的肿瘤标本在这些基因中至少有一个显示异常甲基化。未发现这些基因的甲基化状态与临床参数之间存在显著相关性。
多个基因的甲基化参与了NPC癌症发展的关键途径。然而,RUNX3启动子不存在高甲基化。