Detection of human neurotropic JC virus DNA sequence and expression of the viral oncogenic protein in pediatric medulloblastomas

Detection of human neurotropic JC virus DNA sequence and expression of the viral oncogenic protein in pediatric medulloblastomas
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DOI:
10.1073/pnas.96.20.11519
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发表时间:
1999-09-28
影响因子:
11.1
通讯作者:
Khalili, K
Khalili, K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Krynska, B;Del Valle, L;Khalili, K

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髓母细胞瘤占儿童颅内肿瘤的25%以上,被认为是高度恶性肿瘤。这种肿瘤主要发生在小脑蚓部,优先影响5至15岁的儿童。虽然人类髓母细胞瘤的病因仍不清楚,但几项实验的结果表明,人类嗜神经JC病毒(JCV)能够诱导啮齿动物的小脑肿瘤,表现出与人类髓母细胞瘤相似的表型。JCV是一种多瘤病毒,在人群中广泛存在,感染最常发生在幼儿期。在这项研究中,我们研究了JCV与人类髓母细胞瘤的可能关联。通过PCR技术,证实23例肿瘤组织中有11例含有对应于JCV基因组三个不同区域的DNA序列。更重要的是,我们证明存在的DNA序列编码的N-和C-末端区域的JCV致癌蛋白,T抗原,在11 23个样品和生产的T抗原的细胞核中的4个样品的肿瘤组织。这些观察结果为JCV与人髓母细胞瘤的可能关联提供了证据。
Medulloblastoma represents greater than 25% of childhood intracranial neoplasms and is considered a highly malignant tumor. This tumor, which arises predominantly in the cerebellar vermis, preferentially affects children between the ages of 5 and 15. Although the etiology of medulloblastomas in humans remains unknown, results from several experiments have indicated that the human neurotropic JC virus (JCV) is able to induce cerebellar neoplasms in rodents that exhibit a phenotype similar to that of human medulloblastomas. JCV is a polyomavirus that is widespread in the human population, with infection occurring most frequently in early childhood. In this study, we have examined the possible association of JCV with human medulloblastomas. By using PCR techniques,ve demon strate that 11 of 23 samples of tumor tissue contain DNA sequences corresponding to three different regions of the JCV genome. More importantly we demonstrate the presence of DNA sequences encoding the N- and C-terminal regions of the JCV oncogenic protein, T antigen, in 11 of 23 samples and the production of T antigen in the nuclei of 4 samples of tumor tissue. These observations provide evidence for a possible association of JCV with human medulloblastomas.