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PTEN基因启动子区异常的CpG岛甲基化是鼻咽癌发生的早期事件及潜在的诊断生物标志物。

Aberrant CpG island methylation of PTEN is an early event in nasopharyngeal carcinoma and a potential diagnostic biomarker.

作者信息

Li Jinbang, Gong Pinggui, Lyu Xiaoming, Yao Kaitai, Li Xin, Peng Hong

机构信息

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Cancer Research Institute and the Provincial Key Laboratory of Functional Proteomics, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

出版信息

Oncol Rep. 2014 May;31(5):2206-12. doi: 10.3892/or.2014.3061. Epub 2014 Mar 5.

DOI:10.3892/or.2014.3061
PMID:24604064
Abstract

The inactivation of phosphatase and tensin homolog (PTEN) due to its CpG island hypermethylation has been observed in some types of tumors except nasopharyngeal carcinoma (NPC). In the present study, we focused on the aberrant methylation of PTEN CpG islands in NPC. The mRNA expression of PTEN was detected by quantitative PCR in 45 NPC and 22 non-tumor nasopharyngeal epithelial (NP) tissues. The methylation status of PTEN was examined by methylation-specific polymerase chain reaction and sequencing. The mRNA expression of PTEN in three NPC cell lines treated with 5-aza-2'-deoxycytidine (5-aza-dC) was also examined. PTEN was downregulated in both NPC tissues and NPC cell lines and a relatively higher methylation level of PTEN was found in NPC specimens (82.2%) relative to NP tissues (5.3%). The PTEN mRNA expression was restored in NPC cell lines by treatment with 5-aza-dC. These results first reveal an epigenetic alteration, aberrant methylation of PTEN, in NPC, which is probably an early event and may be regarded as a novel candidate biomarker for early stage of NPC detection and prevention.

摘要

除鼻咽癌(NPC)外,在某些类型的肿瘤中已观察到由于磷酸酶和张力蛋白同源物(PTEN)的CpG岛高甲基化导致其失活。在本研究中,我们聚焦于NPC中PTEN CpG岛的异常甲基化。通过定量PCR检测了45例NPC组织和22例非肿瘤鼻咽上皮(NP)组织中PTEN的mRNA表达。通过甲基化特异性聚合酶链反应和测序检测PTEN的甲基化状态。还检测了用5-氮杂-2'-脱氧胞苷(5-aza-dC)处理的三种NPC细胞系中PTEN的mRNA表达。PTEN在NPC组织和NPC细胞系中均下调,并且相对于NP组织(5.3%),在NPC标本中发现PTEN的甲基化水平相对较高(82.2%)。用5-aza-dC处理后,NPC细胞系中PTEN的mRNA表达得以恢复。这些结果首次揭示了NPC中一种表观遗传改变,即PTEN的异常甲基化,这可能是一个早期事件,并且可被视为NPC早期检测和预防的一种新型候选生物标志物。

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