Detection of human neurotropic JCPyV DNA sequence in pediatric anaplastic xanthoastrocytoma.

Detection of human neurotropic JCPyV DNA sequence in pediatric anaplastic xanthoastrocytoma.
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DOI:
10.1007/s13365-023-01129-z
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发表时间:
2023-04
影响因子:
3.2
通讯作者:
Pietropaolo, Valeria
Pietropaolo, Valeria
中科院分区:
医学4区
文献类型:
--
作者:
Passerini, Sara;Prezioso, Carla;Prota, Annalisa;Babini, Giulia;Bargiacchi, Lavinia;Bartolini, Daniela;Moens, Ugo;Antonelli, Manila;Pietropaolo, Valeria

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多形性黄色星形细胞瘤(PXA)是一种少见的年轻人脑肿瘤,生长缓慢,预后良好,因其独特的组织病理学表现,类似于由JC多瘤病毒(JC PolyomaVirus,JCPyV)引起的致命性神经退行性疾病--进行性多灶性白质脑病的溶血期。因此,利用扩增大T抗原(LTAg)N末端和C末端区域(LTAg)、非编码控制区(NCCR)和病毒蛋白1(VP1)DNA的序列的定量聚合酶链式反应(QPCR)和套式聚合酶链式反应(NPCR),对1例11岁的黄色星形细胞瘤患者进行了JCPyV DNA的检测。LTAg和VP1基因的转录本的表达也被评估。此外,还对病毒microRNAs(MiRNAs)的表达进行了研究。同时在DNA和RNA水平上搜索细胞内的P53。定量聚合酶链式反应检测到JCPyVDNA,其平均值为6.0 × 104gEq/m L。NPCRLTAg基因5ʹ区和NCCR均为阳性,而3个ʹ末端LTAg和VP1DNA序列均不能扩增。仅检测到5个ʹ末端的LTAg转录本,而未检测到VP1基因转录本。虽然在大多数情况下,已经发现Mad-1或Mad-4 NCCR与JCPyV阳性的人脑肿瘤有关,但在患者的样本中观察到了NCCR的原型结构。未检测到病毒miRNA、miR-J1-5p和p53 DNA及RNA。尽管LTAg的表达支持JCPyV在PXA中的可能作用,但黄色星形细胞瘤的发生是否依赖于Rb隔离对LTAg的转化能力,仍需进一步研究。
Due to its peculiar histopathological findings, pleomorphic xanthoastrocytoma (PXA), a rare cerebral tumor of young adults with a slow growth and a good prognosis, resembles to the lytic phase of progressive multifocal leukoencephalopathy, a fatal neurodegenerative disease caused by JC polyomavirus (JCPyV). Therefore, the presence of JCPyV DNA was examined in an 11-year-old child with xanthoastrocytoma, WHO grade 3, by quantitative PCR (qPCR) and nested PCR (nPCR) using primers amplifying sequences encoding the N- and C-terminal region of large T antigen (LTAg), the non-coding control region (NCCR), and viral protein 1 (VP1) DNA. The expression of transcripts from LTAg and VP1 genes was also evaluated. In addition, viral microRNAs’ (miRNAs) expression was investigated. Cellular p53 was also searched at both DNA and RNA level. qPCR revealed the presence of JCPyV DNA with a mean value of 6.0 × 104 gEq/mL. nPCR gave a positive result for the 5ʹ region of the LTAg gene and the NCCR, whereas 3ʹ end LTAg and VP1 DNA sequences were not amplifiable. Only LTAg transcripts of 5ʹ end were found whereas VP1 gene transcript was undetectable. Although in most cases, either Mad-1 or Mad-4 NCCRs have been identified in association with JCPyV-positive human brain neoplasms, the archetype NCCR structure was observed in the patient’s sample. Neither viral miRNA miR-J1-5p nor p53 DNA and RNA were detected. Although the expression of LTAg supports the possible role of JCPyV in PXA, further studies are warranted to better understand whether the genesis of xanthoastrocytoma could depend on the transformation capacity of LTAg by Rb sequestration.
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发表时间: 1999-09-28
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