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检测人类中枢神经系统肿瘤中的 Merkel 细胞多瘤病毒大 T 抗原序列。

Detection of Merkel cell polyomavirus large T-antigen sequences in human central nervous system tumors.

机构信息

Department of Virology, Tehran University of Medical Sciences, School of Public Health, Tehran, Iran; Department of Immunology and Microbiology, Babol University of Medical Sciences, School of Medicine, Babol, Iran.

出版信息

J Med Virol. 2015 Jul;87(7):1241-7. doi: 10.1002/jmv.24178. Epub 2015 Mar 9.

DOI:10.1002/jmv.24178
PMID:25754536
Abstract

Despite decades of epidemiological investigation, little is known about the etiology of the central nervous system (CNS) tumors, and few well-established risk factors have been recognized. This study tested the presence of Merkel cell polyomavirus (MCPyV), the only member of the Polyomaviridae family convincingly linked to human cancer, in diverse CNS malignancies. In total, 58 CNS tumor biopsies were analyzed for the MCPyV large T-antigen (LT-Ag) gene by quantitative real-time PCR. Merkel cell polyomavirus LT-Ag DNA load was determined as viral copies per cell and viral copies per microliter of purified genomic DNA from CNS tumor samples. The MCPyV LT-Ag sequence was detected in 34 (58.6%) of the 58 tested samples. Viral LT-Ag was quantified in 19.0% of schwannomas, 13.8% of meningiomas, and 5.2% of pituitary adenomas. The difference between MCPyV positivity in different types of CNS malignancies was not statistically significant (P = 0.066). The mean LT-Ag copy number in 34 positive samples was 744.5 ± 737.7 and 0.056 × 10(-3)  ± 0.091 × 10(-3) per microliter and per cell, respectively. Among MCPyV-positive CNS tumors, the mean MCPyV copy number was higher in meningiomas (993.8 ± 853.2 copy per microliter and 0.098 × 10(-3)  ± 0.108 × 10(-3) copy per cell). Multiple linear regression analysis revealed statistically significant difference in MCPyV copy number between meningioma and other CNS tumor types, when the model was adjusted for age and sex (P = 0.024). This study shows the first evidence of the detection of MCPyV LT-Ag sequence at a low copy number in human CNS tumors.

摘要

尽管经过了几十年的流行病学研究,但人们对中枢神经系统 (CNS) 肿瘤的病因仍知之甚少,并且仅识别出少数明确的危险因素。本研究检测了默克尔细胞多瘤病毒(MCPyV)在多种 CNS 恶性肿瘤中的存在,MCPyV 是唯一一种与人类癌症密切相关的多瘤病毒科病毒。总共分析了 58 例 CNS 肿瘤活检,通过定量实时 PCR 检测 MCPyV 大 T 抗原(LT-Ag)基因。Merkel 细胞多瘤病毒 LT-Ag DNA 载量通过病毒拷贝数/细胞和 CNS 肿瘤样本纯化基因组 DNA 中的病毒拷贝数/微升来确定。在 58 个测试样本中,有 34 个(58.6%)检测到 MCPyV LT-Ag 序列。神经鞘瘤、脑膜瘤和垂体腺瘤的病毒 LT-Ag 定量分别为 19.0%、13.8%和 5.2%。不同类型的 CNS 恶性肿瘤之间的 MCPyV 阳性率差异无统计学意义(P=0.066)。34 个阳性样本的平均 LT-Ag 拷贝数分别为 744.5±737.7 和 0.056×10(-3)±0.091×10(-3) /μl 和 /细胞。在 MCPyV 阳性的 CNS 肿瘤中,脑膜瘤的 MCPyV 拷贝数较高(993.8±853.2 拷贝/μl 和 0.098×10(-3)±0.108×10(-3) 拷贝/细胞)。多元线性回归分析显示,在调整年龄和性别后,脑膜瘤与其他 CNS 肿瘤类型的 MCPyV 拷贝数存在统计学差异(P=0.024)。本研究首次证明了在人类 CNS 肿瘤中以低拷贝数检测到 MCPyV LT-Ag 序列。

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