High human cytomegalovirus antigen expression in pediatric medulloblastoma tissue is associated with poor event-free survival
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Updated: May 5, 2026
Intracranial Orthotopic Allografting of Medulloblastoma Cells in Immunocompromised Mice
Published on: October 3, 2010
Maria F De la Cerda-Vargas1,2, Jens Schittenhelm3, Martin Ebinger4
1Department of Neurosurgery and Neurotechnology, Universitätsklinik Tübingen, Tübingen.
Background:
Despite advancements in treatment, 5-year survival for medulloblastoma (MB) remains 60%-70%. Human cytomegalovirus (HCMV) has been implicated as an oncomodulator in MB, but its impact on survival has not been explored. This study evaluates HCMV expression in pediatric MB tissue and its association with molecular risk groups and survival.
Methods:
A retrospective study of pediatric MB cases (≤19 years) from 2007 to 2023 was conducted using the WHO 2021 classification, the Northcott brain-tumor classifier, and the SIOP-Europe/ERN PaedCan risk stratification. HCMV immediate-early (HCMV-IE) and late-antigen (HCMV-LA) expression were assessed by optimized immunohistochemistry, and whole-genome sequencing (WGS) data from 20 tumors were analyzed for viral gene expression.
Results:
Forty-five patients (mean age 8.2 years; 22% ≤3 years) were included: WNT (18%), SHH TP53-wildtype (18%), and non-WNT/non-SHH (64%). Twenty percent of MB belonged to low-risk, 33% to standard-risk, and 47% to high-risk (HR-MB) groups. Four tumors exhibited MYC/N amplification. HCMV-LA positivity was found in 84% of cases, with 53% showing high expression (≥25% of cells). Cox-regression identified HR-MB (HR = 4.197, p = .021) and high HCMV-LA (HR = 4.334, p = .027) as independent predictors of poor outcomes. WGS revealed UL88 as the most abundantly expressed HCMV gene (log2[TPM+1] ≈ 14-15), with maximal expression in Group 3 MB.
Conclusions:
This study provides the first evidence linking high HCMV-LA expression to adverse outcomes and high-risk molecular features in pediatric MB. UL88 emerged as the most strongly expressed HCMV gene across MB samples. These findings suggest a potential prognostic and therapeutic role for HCMV in MB, warranting validation in larger, prospective cohorts.
Insights
High human cytomegalovirus (HCMV) late-antigen expression in pediatric medulloblastoma (MB) is linked to poor outcomes. This study identifies HCMV as a potential prognostic marker in high-risk MB.
Area of Science:
- Oncology
- Virology
- Pediatric Medicine
Background:
- Medulloblastoma (MB) survival rates remain suboptimal despite treatment advancements.
- Human cytomegalovirus (HCMV) is suspected to influence MB development, but its prognostic significance is unexplored.
- This study investigates HCMV expression in pediatric MB and its correlation with molecular subtypes and patient outcomes.
Purpose of the Study:
- To evaluate HCMV expression in pediatric medulloblastoma (MB) tissue.
- To determine the association between HCMV expression, molecular risk groups, and patient survival.
- To identify specific HCMV genes expressed in MB and their correlation with molecular subtypes.
Main Methods:
- Retrospective analysis of pediatric MB cases (2007-2023) classified by WHO 2021 and Northcott brain-tumor classifier.
- Immunohistochemistry to assess HCMV immediate-early (HCMV-IE) and late-antigen (HCMV-LA) expression.
- Whole-genome sequencing (WGS) to analyze viral gene expression in 20 MB tumors.
Main Results:
- High HCMV-LA expression (≥25% of cells) was observed in 53% of MB cases.
- High-risk MB (HR-MB) and high HCMV-LA expression were independent predictors of poor outcomes (HR=4.334, p=0.027).
- Whole-genome sequencing identified UL88 as the most abundant HCMV gene, with peak expression in Group 3 MB.
Conclusions:
- This study presents the first evidence linking high HCMV-LA expression to adverse outcomes and high-risk molecular features in pediatric MB.
- UL88 was the most highly expressed HCMV gene in the analyzed MB samples.
- HCMV may play a prognostic and potentially therapeutic role in MB, necessitating further investigation in larger cohorts.
