Lack of cytomegalovirus detection in human glioma

Araceli Garcia-Martinez,Esperanza Irles,Cristina Alenda,Alvaro Rodriguez-Lescure,Victor M Barbera,Enrique Ochoa,Jose L Soto,Teresa Quintanar

doi:10.1186/s12985-017-0885-3

Abstract

Gliomas are the most common brain tumors and include a variety of histologic types and grades of malignancy. They arise from glial cells and represent approximately 70% of the primary brain tumors. According to the criteria of the World Health Organization (WHO), the majority of gliomas can be classified into four grades of malignancy (I-IV). Virus infection, especially by DNA viruses and retroviruses, which may cause insertion of viral DNA sequences into the host genome, often triggers the host defense mechanisms. Particularly, the DNA methylation machinery can be activated to cause the methylation of foreign movable viral sequences and, therefore, silence viral gene expression. Several studies have shown the presence of Human Cytomegalovirus (HCMV) in glioblastoma, suggesting that the virus may participate in tumor pathogenesis. But this relationship is controversial because many other studies did not detect HCMV in these tumors. This study aims to detect the presence of HCMV in several samples of human glioma (94 formalin-fixed, paraffin-embedded samples and 28 snap-frozen samples) by different sensitive techniques. We have been unable to detect HCMV DNA and proteins in glioma samples. Therefore, arguments used so far to conclude that HCMV is an oncomodulator virus in gliomas must be, in our view, seriously reconsidered.

Highlights

Gliomas constitute a heterogeneus group of malignant neoplasms of the central nervous system which are derived from glial cells and represent the most frequent form of primary brain tumors, over 70% of cases [1, 2]
Procedure and results With the aim of shedding light on such uncertainty, we set to analyze in this study a large series of primary gliomas in order to detect the presence of Human Cytomegalovirus (HCMV) by a diagnostic, validated real-time PCR method
A multicenter study is necessary in which a standardized methodology is used to unequivocally determine whether this virus is present in glioma samples

Summary

Introduction

Gliomas constitute a heterogeneus group of malignant neoplasms of the central nervous system which are derived from glial cells and represent the most frequent form of primary brain tumors, over 70% of cases [1, 2]. Gliomas are classified into four malignant grades attending to their morphological and histological features. Glioblastoma multiforme, the most malignant type of glioma (WHO grade IV), is highly aggressive and invasive, with a mean survival rate of 14–15 months after diagnosis. Large epidemiological studies have failed to identify new clear causative factors, in recent years cytomegalovirus infections have focused the scientific community attention. Their etiological role in the genesis of gliomas is currently controversial

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