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

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.

Comprehensive analysis of Iranian reports of pediatric central nervous system tumors

“…Eight reports described whether approval from an ethics committee was obtained [59–60, 64, 66, 69–71, 75]. The majority (58.3%) of patients described in the articles was male [38, 41–50, 52, 56–57, 60–61, 63–64, 67–68, 72–75]. We were unable to determine the number of patients who were children, as most of the reports did not include this information.…”

“…Of the 39 mixed-population studies, 21 were conducted in Tehran province [39–41, 43, 45–46, 48–49, 51–54, 59–61, 64–66, 72–73, 75], specifically at Tehran University of Medical Sciences (n = 16) [39–41, 43, 45–46, 48–49, 51, 59–61, 65–66, 73, 75] or Shahid Beheshti University of Medical Sciences (n = 5) [52–54, 64, 72]. The study objectives were categorized as genetic (n = 9 articles [38, 44, 50, 56, 62, 65–66, 70–71], 449 patients), epidemiologic (n = 7 articles [47, 49, 60–61, 63, 69, 74], 13,193 patients), pathologic (n = 7 articles [46, 48, 52, 55, 67–68, 72], 4,365 patients), clinical (n = 6 articles [39, 41, 43, 45, 57, 76], 393 patients), radiologic (n = 4 articles [, 86 patients), radiotherapy (n = 3 articles [54, 58–59, 73], 54 patients), surgical (n = 2 articles [42, 51], 44 patients), or virologic [75] (n = 1, 58 patients).…”

“…The study objectives were categorized as genetic (n = 9 articles [38, 44, 50, 56, 62, 65–66, 70–71], 449 patients), epidemiologic (n = 7 articles [47, 49, 60–61, 63, 69, 74], 13,193 patients), pathologic (n = 7 articles [46, 48, 52, 55, 67–68, 72], 4,365 patients), clinical (n = 6 articles [39, 41, 43, 45, 57, 76], 393 patients), radiologic (n = 4 articles [, 86 patients), radiotherapy (n = 3 articles [54, 58–59, 73], 54 patients), surgical (n = 2 articles [42, 51], 44 patients), or virologic [75] (n = 1, 58 patients).…”

“…PSI was evaluated in only one study [41], which was reported in 2004. Seven articles described the follow-up of patients [41, 51, 53, 57, 64–65, 75]. …”

No Evidence for an Association between JC Polyomavirus Infection and Gastroduodenal Diseases

“…The JCPyV LTag DNA load was determined as the viral DNA copies/RNase P gene copy (a proven single copy gene), which described the copy number/cell. Construction of plasmids containing cloned target sequences of JCPyV LTag and human RNase P gene (quantitative standards for real-time PCR) was described previously [27,28]. Quantitative real-time PCR was conducted using a Rotor-Gene ® Q (Qiagen GmbH, Hilden, Germany) real-time PCR system by the primer sets and TaqMan probe specific for the JCPyV LTag gene and the human RNase P gene according to a previously described procedure [29,30].…”