儿童恶性成黄色星形胶质瘤中检测到人类神经病毒JC型病毒DNA序列。
Detection of human neurotropic JCPyV DNA sequence in pediatric anaplastic xanthoastrocytoma.
发表日期:2023 Apr 25
作者:
Sara Passerini, Carla Prezioso, Annalisa Prota, Giulia Babini, Lavinia Bargiacchi, Daniela Bartolini, Ugo Moens, Manila Antonelli, Valeria Pietropaolo
来源:
Brain Structure & Function
摘要:
由于其特异的组织病理学发现,多形性黄色星形胶质瘤(PXA)与JC多瘤病毒(JCPyV)引起的致命神经退行性疾病进行性多灶性白质脑病(PML)的毁灭性期相似,后者是一种年轻成人的罕见脑肿瘤,生长缓慢且预后良好。因此,使用扩增编码大T抗原(LTAg)的N-和C-末端区域、非编码控制区域(NCCR)和病毒蛋白1(VP1)DNA的引物进行定量PCR(qPCR)和巢式PCR(nPCR),检测了一个11岁的患有WHO III级黄色星形胶质瘤的儿童体内是否存在JCPyV DNA。还评估了LTAg和VP1基因的转录本表达情况。此外,还研究了病毒microRNA(miRNA)的表达以及细胞p53在DNA和RNA水平的搜索。qPCR检测到JCPyV DNA的存在,平均值为6.0×104 gEq/mL。nPCR针对LTAg基因的5’区域和NCCR给出了阳性结果,而3'端LTAg和VP1 DNA序列则无法扩增。只发现了5'端LTAg的转录本,而VP1基因转录本无法检测。虽然在大多数情况下,JCPyV阳性的人脑肿瘤与Mad-1或Mad-4 NCCR有关,但在患者样本中观察到了原型NCCR结构。没有检测到病毒miRNA miR-J1-5p或p53 DNA和RNA。虽然LTAg的表达支持JCPyV在PXA中的可能作用,但有必要进行进一步的研究,以更好地了解黄色星形胶质瘤的起源是否取决于由Rb滞留引起的LTAg的转化能力。© 2023年作者。
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 5' region of the LTAg gene and the NCCR, whereas 3' end LTAg and VP1 DNA sequences were not amplifiable. Only LTAg transcripts of 5' 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.© 2023. The Author(s).