Human cytomegalovirus DNA detection in a recurrent glioblastoma multiforme tumour, but not in whole blood: a case report

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CASE REPORT

Human cytomegalovirus DNA detection in a recurrent glioblastoma multiforme tumour, but not in whole blood: a case report and discussion about the HCMV latency and therapy perspectives Emiliya Nikolova 1,2

&

Petia Dimova 3 & Krasimir Minkin 4 & Tihomir Todorov 2 & Vanio Mitev 1 & Albena Todorova 1,2

Received: 17 May 2020 / Revised: 1 August 2020 / Accepted: 21 August 2020 # Journal of NeuroVirology, Inc. 2020

Abstract In the current study, a 58-year-old male patient presented with recurrent glioblastoma multiforme (GBM). The patient underwent surgical resection, 4 months earlier, followed by radiotherapy and chemotherapy. During the second surgical intervention, tumour tissue and whole blood were sampled and analysed for human cytomegalovirus (HCMV) DNA, immediate early (IE) mRNA and pp65 mRNA. HCMV DNA was detected only in the recurrent tumour tissue but not in the whole blood. Neither IE mRNA nor pp65 mRNA was expressed. Our result suggests HCMV latency in the brain tumour with detectable level of viral DNA. More data are needed to understand the HCMV infection chronology in the brain tumours but our data could be important for further studies of HCMV antigens on the tumour surface and anti-GBM therapy. Keywords Human cytomegalovirus . Glioblastoma multiforme . Anti-tumour therapy

Introduction In the past decades, the role of HCMV infection in the development and progression of brain tumours became a source of scientific research and debate. Even during the latency, HCMV is able to modify the oncogenic phenotype of the cell, through the so-called mechanism of oncomodulation by disturbing critical signalling pathways (Cinatl et al. 1996). Primary and secondary brain tumours have been found positive for HCMV proteins and nucleic acids, but adjacent nontumoral brain tissue was negative (Cobbs et al. 2002; Mitchell et al. 2008). Moreover, GBM patients with low viral blood load have longer OS time compared with patients with high viral blood load (Rahbar et al. 2013).

The aim of our study is to present a case report of Bulgarian patient with recurrent GBM and detection of HCMV DNA only in the tumour tissue but not in whole blood. Additionally, the analysis of viral immediate early (IE) protein mRNA and pp65 mRNA showed lack of expression. Our result suggests HCMV latency in the brain tumour with detectable level of viral DNA. There are not enough data of HCMV latency in the brain tumours but our data could be important for further analyses of HCMV antigens on the tumour cell surface and the development of targeted antiHCMV and anti-GBM therapy.

Case report * Emiliya Nikolova [email protected] 1

Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University – Sofia, Sofia, Bulgaria

2

Genetic Medico-Diagnostic Laboratory “Genica”, Sofia, Bulgaria

3

Epilepsy Center, Department of Neurosurgery, University Hospital ‘St. Ivan Rilski’, Sofia, Bulgaria

4

Department of Neurosurgery, University Hospital ‘St. Ivan Rilski’, Sofia, Bulgaria

A 58-year-old man was diagnosed wi