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.
Similar content being viewed by others
References
Batich KA, Reap EA, Archer GE, Sanchez-Perez L, Nair SK, Schmittling RJ, Norberg P, Xie W, Herndon JE 2nd, Healy P, McLendon RE, Friedman AH, Friedman HS, Bigner D, Vlahovic G, Mitchell DA, Sampson JH (2017) Long-term survival in glioblastoma with cytomegalovirus pp65-targeted vaccination. Clin Cancer Research 23:1898–1909. https://doi.org/10.1158/1078-0432.CCR-16-2057
Cinatl J Jr, Cinatl J, Vogel JU, Rabenau H, Kornhuber B, Doerr HW (1996) Modulatory effects of human cytomegalovirus infection on malignant properties of cancer cells. Intervirology 39:259–269. https://doi.org/10.1159/000150527
Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, Nabors LB, Cobbs CG, Britt WJ (2002) Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res 62:3347–3350
Duan YL, Ye HQ, Zavala AG, Yang C, Miao L, Fu B, Seo K, Davrinche C, Luo M, Fortunato E (2014) Maintenance of large numbers of virus genomes in human cytomegalovirus-infected T98G glioblastoma cells. J Virol 88(7):3861–3873. https://doi.org/10.1128/JVI.01166-13
Hadaczek P, Ozawa T, Soroceanu L, Yoshida Y, Matlaf L, Singer E, Fiallos E, James CD, Cobbs CS (2013) Cidofovir: a novel antitumor agent for glioblastoma. Clin Cancer Res 19:6473–6483. https://doi.org/10.1158/1078-0432.CCR-13-1121
Kala R, Shah HN, Martin SL, Tollefsbol TO (2015) Epigenetic-based combinatorial resveratrol and pterostilbene alters DNA damage response by affecting SIRT1 and DNMT enzyme expression, including SIRT1-dependent γ-H2AX and telomerase regulation in triple-negative breast cancer. BMC Cancer 15:672. https://doi.org/10.1186/s12885-015-1693-z
Lehrer S, Green S, Rosenzweig KE, Rendo A (2015) No circulating human cytomegalovirus in 14 cases of glioblastoma. Neuro-Oncology 17:320. https://doi.org/10.1093/neuonc/nou325
Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A, McLendon RE, Sampson JH (2008) Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro-Oncology 10:10–18. https://doi.org/10.1215/15228517-2007-035
Orringer D, Lau D, Khatri S, Zamora-Berridi GJ, Zhang K, Wu C, Chaudhary N, Sagher O (2012) Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival. J Neurosurg 117:851–859. https://doi.org/10.3171/2012.8.JNS12234
Plummer M, de Martel C, Vignat J (2016) Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Heal 4:609–616. https://doi.org/10.1016/S2214-109X(16)30143-7
Rahbar A, Orrego A, Peredo I, Dzabic M, Wolmer-Solberg N, Straat K, Stragliotto G, Soderberg-Naucler C (2013) Human cytomegalovirus infection levels in glioblastoma multiforme are of prognostic value for survival. J Clin Virol 57:36–42. https://doi.org/10.1016/j.jcv.2012.12.018
Revello MG, Lilleri D, Zavattoni M, Stronati M, Bollani L, Middeldorp J, Gerna G (2001) Human cytomegalovirus immediate-early messenger RNA in blood of pregnant women with primary infection and of congenitally infected newborns. The Journal of Infectious Diseases 184:1078–1081. https://doi.org/10.1086/323425
Schneider M, Reitter EM, Kastner MT, Thannesberger J, Rieder F, Preusser M, Marosi C, Steininger C (2017) Absence of CMV viremia in high-grade glioma patients under low dose glucocorticoid treatment. Neuro-Oncology 19:1280–1282. https://doi.org/10.1093/neuonc/nox065
Schuessler A, Smith C, Beagley L, Boyle GM, Rehan S, Matthews K, Jones L, Crough T, Dasari V, Klein K, Smalley A, Alexander H, Walker DG, Khanna R (2014) Autologous T-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma. Cancer Res 74:3466–3476. https://doi.org/10.1158/0008-5472.CAN-14-0296
See AP, Parker JJ, Waziri A (2015) The role of regulatory T cells and microglia in glioblastoma-associated immunosuppression. J Neuro-Oncol 123:405–412. https://doi.org/10.1007/s11060-015-1849-3
Soroceanu L, Matlaf L, Khan S, Akhavan A, Singer E, Bezrookove V, Decker S, Ghanny S, Hadaczek P, Bengtsson H, Ohlfest J, Luciani-Torres MG, Harkins L, Perry A, Guo H, Soteropoulos P, Cobbs CS (2015) Cytomegalovirus immediate-early proteins promote stemness properties in glioblastoma. Cancer Res 75:3065–3076. https://doi.org/10.1158/0008-5472.CAN-14-3307
Stragliotto G, Rahbar A, Solberg NW, Lilja A, Taher C, Orrego A, Bjurman B, Tammik C, Skarman P, Peredo I, Söderberg-Nauclér C (2013) Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: a randomized, double-blind, hypothesis-generating study. Int J Cancer 133:1204–1213. https://doi.org/10.1002/ijc.28111
Tsutsui Y, Kawasaki H, Kosugi I (2002) Reactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice cultures. J Virol 76(14):7247–7254
Acknowledgements
We thank Teodora Tasseva from Institute of Plant Physiology and Genetics – Bulgarian Academy of Sciences, Slavena Atemin and Zornitsa Pavlova from Genetic Medico-Diagnostic Laboratory “Genica”, Sofia, Bulgaria.
Funding
This work was supported in part by Medical University – Sofia, grants D-118/2018 and D-127/2019.
Author information
Authors and Affiliations
Contributions
All authors approved the contents of the manuscript and validated the accuracy of the data.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Nikolova, E., Dimova, P., Minkin, K. et al. 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. J. Neurovirol. 26, 984–987 (2020). https://doi.org/10.1007/s13365-020-00901-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13365-020-00901-9