在不同民族的以色列结直肠癌患者的肿瘤组织中检测到 hMLH1 启动子甲基化和 JCV T 抗原。

hMLH1 promoter methylation and JC virus T antigen presence in the tumor tissue of colorectal cancer Israeli patients of different ethnic groups.

机构信息

Department of Gastroenterology, Rabin Medical Center, Beilinson Hospital, and Tel Aviv University, Israel.

出版信息

Eur J Gastroenterol Hepatol. 2010 Aug;22(8):938-41. doi: 10.1097/MEG.0b013e32832e9d2c.

DOI:10.1097/MEG.0b013e32832e9d2c

PMID:20531010

Abstract

BACKGROUND

Hypermethylation of tumor suppressor genes' promoter and JC virus infection may be etiologic factors in the development of colorectal cancer (CRC).

OBJECTIVES

To look at both JC virus T antigen and hMLH1 promoter methylation in CRC tissue in Israeli ethnic groups with different incidence of CRC.

METHODS

Twenty-four consecutive patients with sporadic CRC were included in the study. Genomic DNA was isolated from paraffin-embedded microdomains removed from five slides of 7 mum by deparaffinizing in multiple xylene washes. Isolated DNA was used as a template for PCR to amplify DNA sequences coding the amino terminus of JC virus T antigen. Methylation-specific PCR was performed on bisulfite-modified DNA templates from CRC tissue materials to study methylation status of hMLH1 promoter, using two sets of primers specific for amplification of methylated and unmethylated alleles.

RESULTS

hMLH1 promoter methylation was observed in five patients (20.8%) who were also positive for JC virus T antigen, with even distribution among the ethnic groups. JC virus T antigen DNA was found in cancer tissues of 20 of the 24 patients; 50, 90.9, and 100% of Asia-Africa-born Jews, Europe-America-born Jews, and Israeli Arabs, respectively (P = 0.036 between the first group to the other).

CONCLUSION

Evidence for higher JC virus infection was shown among Europe-America-born Jews and Israeli Arabs. hMLH1 promoter methylation was evenly distributed between different ethnic groups in Israel.

摘要

背景

肿瘤抑制基因启动子的高甲基化和 JC 病毒感染可能是结直肠癌（CRC）发展的病因。

目的

观察不同 CRC 发病率的以色列种族中 CRC 组织中的 JC 病毒 T 抗原和 hMLH1 启动子甲基化。

方法

纳入 24 例连续的散发性 CRC 患者。从 5 张 7 微米的载玻片上的微区去除石蜡，用多次二甲苯洗涤进行脱蜡，从石蜡包埋的微区中分离出基因组 DNA。分离的 DNA 用作 PCR 的模板，以扩增编码 JC 病毒 T 抗原氨基末端的 DNA 序列。使用两对用于扩增甲基化和非甲基化等位基因的引物，对 CRC 组织材料的亚硫酸氢盐修饰的 DNA 模板进行甲基化特异性 PCR，以研究 hMLH1 启动子的甲基化状态。

结果

5 例（20.8%）患者 hMLH1 启动子甲基化，同时 JC 病毒 T 抗原阳性，各民族分布均匀。24 例患者中有 20 例的癌症组织中发现了 JC 病毒 T 抗原；出生于亚洲-非洲的犹太人、欧洲-美洲出生的犹太人、以色列阿拉伯人分别为 50%、90.9%和 100%（第一组与其他两组之间的 P = 0.036）。