Widschwendter Andreas, Müller Hannes M, Hubalek Michael M, Wiedemair Annemarie, Fiegl Heidi, Goebel Georg, Mueller-Holzner Elisabeth, Marth Christian, Widschwendter Martin
Department of Obstetrics and Gynecology, Innsbruck University Hospital, A-6020 Innsbruck, Austria.
Gynecol Oncol. 2004 May;93(2):407-16. doi: 10.1016/j.ygyno.2004.01.036.
Activation of telomerase, the enzyme that synthesizes the telomere ends of linear chromosomes, has been implicated in human cell immortalization and cancer cell pathogenesis. The expression pattern of human telomerase reverse transcriptase (hTERT), the telomerase catalytic subunit gene, is correlated with telomerase activity. The promotor region of the hTERT gene has been located in a CpG island and may therefore be regulated, at least in part, by DNA methylation. The potential for methylation-mediated regulation of hTERT gene expression in ovarian and cervical cancer tissue has not been investigated up to now. The aim of this study was to investigate the expression and methylation pattern of hTERT in ovarian and cervical cancer tissue and their correlation with clinicopathological features and outcome of the disease.
A total of 223 tissues were analyzed for hTERT methylation using MethyLight: 65 patients with cervical cancer and 124 with ovarian cancer were studied. The control group consisted of 20 normal ovarian tissues and 14 normal cervical tissues. Quantitative hTERT expression analysis was carried out in a subgroup of patients using real time PCR.
hTERT expression was statistically significantly higher in ovarian and cervical cancer tissue in comparison to normal tissue. While methylation of hTERT in cervical cancer was significantly more frequent in comparison to normal cervical tissue, the difference between ovarian cancer and normal ovarian tissue was not significant. No correlation was detected between hypermethylation of hTERT and hTERT mRNA expression. Both ovarian cancer and normal ovary showed an increase in hTERT methylation with increasing age. hTERT expression was not correlated with prognosis, whereas cervical and ovarian cancer patients with unmethylated hTERT had significantly better overall survival.
At least in some tumor entities, hTERT methylation is a function of age and is associated with a poorer outcome, irrespective of hTERT expression.
端粒酶可合成线性染色体的端粒末端，其激活与人类细胞永生化及癌细胞发病机制有关。人类端粒酶逆转录酶（hTERT）是端粒酶的催化亚基基因，其表达模式与端粒酶活性相关。hTERT基因的启动子区域位于一个CpG岛，因此可能至少部分受DNA甲基化调控。目前尚未研究卵巢癌和宫颈癌组织中hTERT基因表达的甲基化介导调控潜力。本研究旨在探讨hTERT在卵巢癌和宫颈癌组织中的表达及甲基化模式，及其与临床病理特征和疾病预后的相关性。
使用MethyLight对总共223个组织进行hTERT甲基化分析：研究了65例宫颈癌患者和124例卵巢癌患者。对照组由20个正常卵巢组织和14个正常宫颈组织组成。对部分患者亚组进行实时PCR定量hTERT表达分析。
与正常组织相比，卵巢癌和宫颈癌组织中hTERT表达在统计学上显著更高。与正常宫颈组织相比，宫颈癌中hTERT甲基化明显更频繁，而卵巢癌与正常卵巢组织之间的差异不显著。未检测到hTERT高甲基化与hTERT mRNA表达之间的相关性。卵巢癌和正常卵巢组织均显示hTERT甲基化随年龄增加而增加。hTERT表达与预后无关，而hTERT未甲基化的宫颈癌和卵巢癌患者总生存期明显更好。
至少在某些肿瘤实体中，hTERT甲基化是年龄的函数，且与较差的预后相关，与hTERT表达无关。
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