Human Cytomegalovirus DNA Quantification and Gene Expression in Gliomas of Different Grades.

Lucas Matheus Stangherlin,Fabiane Lucy Ferreira Castro,Maria Cristina Carlan Silva,Neuza Kazumi Shirata,Claudia Januário dos Santos,Suely Nonogaki,Raphael Salles Scortegagna Medeiros,Lidia Midori Kimura,Juliana Mariotti Guerra,Michael Nevels

doi:10.1371/journal.pone.0159604

Abstract

Gliomas are the most common type of primary brain tumors. The most aggressive type, Glioblastoma multiforme (GBM), is one of the deadliest human diseases, with an average survival at diagnosis of about 1 year. Previous evidence suggests a link between human cytomegalovirus (HCMV) and gliomas. HCMV has been shown to be present in these tumors and several viral proteins can have oncogenic properties in glioma cells. Here we have investigated the presence of HCMV DNA, RNA and proteins in fifty-two gliomas of different grades of malignancy. The UL83 viral region, the early beta 2.7 RNA and viral protein were detected in 73%, 36% and 57% by qPCR, ISH and IHC, respectively. Positivity of the viral targets and viral load was independent of tumor type or grade suggesting no correlation between viral presence and tumor progression. Our results demonstrate high prevalence of the virus in gliomas from Brazilian patients, contributing to a better understanding of the association between HCMV infection and gliomas worldwide and supporting further investigations of the virus oncomodulatory properties.

Highlights

Gliomas are the most common intra axial brain tumors in adults, representing 40 to 60% of primary central nervous system (CNS) tumors[1], with an annual incidence of 5/100,000 individuals
To investigate the expression of human cytomegalovirus (HCMV) RNA and protein in the tumors we performed in situ hybridization (ISH), using a probe for the early beta 2.7 transcript and immunohistochemistry (IHC), using an antibody that recognizes a HCMV nuclear protein
The association of HCMV with gliomas has been a topic greatly debated in the brain tumor field

Summary

Introduction

Gliomas are the most common intra axial brain tumors in adults, representing 40 to 60% of primary central nervous system (CNS) tumors[1], with an annual incidence of 5/100,000 individuals. According to the World Health Organization (WHO) classification of CNS tumors, gliomas are divided in ependymomas, astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. This universal classification system considers the morphology of tumor cells, tissue architecture, and immunohistological marker profiles [2]. Based on malignant tumor behavior astrocytomas are divided in pilocytic (AST I), diffuse (AST II), anaplastic (AST III) and glioblastoma multiforme (GBM) (AST IV). Oligodendrogliomas are divided in grade II (ODG II) or III (ODG III) [3].

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Results

Conclusion