Jakob C A, Guldenschuh I, Hürlimann R, Müllhaupt B, Müller A, Ammann R, Fried M, Roth J
Department of Pathology, University of Zurich, Switzerland.
Virchows Arch. 1999 Jan;434(1):57-62. doi: 10.1007/s004280050305.
DNA methylation plays an important part in the regulation of gene expression. Alterations in DNA methylation in tumours have been reported and have been used to generate hypotheses about mutagenesis and silencing of tumour suppressor genes. However, the underlying mechanism is still poorly understood, and conflicting data on the levels of overexpression of 5'-cytosine DNA methyltransferase in sporadic colon carcinoma have been published. We used a competitive RT-PCR assay for quantification of mRNA of 5'-cytosine DNA methyltransferase in colon biopsies obtained from patients with hereditary colon carcinoma syndromes and compared the results with those obtained in a control group. No significant difference was found between the flat mucosa of FAP patients and the mucosa of the control group. In FAP and HNPCC patients, the 5'-cytosine DNA methyltransferase mRNA levels of adenomas were significantly higher (P<0.05) than of flat mucosa in the same group, but both showed great variability from patient to patient. Our findings suggest that the mRNA levels of methyltransferase cannot be used as predictive marker for screening in families affected by hereditary colon carcinoma.
DNA甲基化在基因表达调控中起重要作用。肿瘤中DNA甲基化的改变已有报道,并被用于生成关于肿瘤抑制基因突变和沉默的假说。然而,其潜在机制仍知之甚少,且关于散发性结肠癌中5'-胞嘧啶DNA甲基转移酶过表达水平的相互矛盾的数据也已发表。我们使用竞争性逆转录-聚合酶链反应(RT-PCR)分析法对遗传性结肠癌综合征患者的结肠活检组织中5'-胞嘧啶DNA甲基转移酶的mRNA进行定量,并将结果与对照组进行比较。在家族性腺瘤性息肉病(FAP)患者的扁平黏膜与对照组黏膜之间未发现显著差异。在FAP和遗传性非息肉病性结直肠癌(HNPCC)患者中,腺瘤的5'-胞嘧啶DNA甲基转移酶mRNA水平显著高于(P<0.05)同组的扁平黏膜,但两者在患者之间均表现出很大的变异性。我们的研究结果表明,甲基转移酶的mRNA水平不能用作遗传性结肠癌受累家族筛查的预测标志物。