Abstract
BackgroundAccounting for 15–20% of all meningiomas, WHO grade II meningiomas represent an intermediate group regarding risk of tumor recurrence. However, even within this subgroup varying clinical courses are observed with potential occurrence of multiple recurrences. Recently, DNA methylation profiles showed their value for distinguishing biological behaviors in meningiomas. Therefore, aim of this study was to investigate DNA methylation profiles in WHO grade II meningiomas.MethodsAll patients that underwent resection of WHO grade II meningiomas between 1993 and 2015 were screened for a dismal course clinical course with ≥2 recurrences. These were matched to control cases with benign clinical courses without tumor recurrence. DNA methylation was assessed using the Infinium Methylation EPIC BeadChip microarray. Unsupervised hierarchical clustering was performed for identification of DNA methylation profiles associated with such a dismal clinical course.ResultsOverall, 11 patients with WHO grade II meningiomas with ≥2 recurrences (Group dismal) and matched 11 patients without tumor recurrence (Group benign) were identified. DNA methylation profiles revealed 3 clusters—one comprising only patients of group dismal, a second cluster comprising mainly patients from group benign and a third cluster comprising one group dismal and one group benign patient. Based on differential methylation pattern associations with the Wnt and the related cadherin signaling pathway was observed.ConclusionDNA methylation clustering showed remarkable differences between two matched subgroups of WHO grade II meningiomas. Thus, DNA methylation profiles may have the potential to support prognostic considerations regarding meningioma recurrence and radiotherapeutic treatment allocation after surgical resection.
Highlights
More than 30% of intracranial CNS tumors represent meningiomas which are considered slowly growing tumors in the majority of cases [1, 2]
Of all 1,675 patients who underwent surgical resection of a newly diagnosed meningioma, an atypical World Health Organization (WHO) grade II meningioma was diagnosed in 179 patients (10.7%)
Despite assumed complete tumor removal and similar radiologic and histopathologic appearance, the clinical courses of WHO grade II meningiomas can present in clinical practice in a very heterogeneous pattern: while some of these patients never develop tumor recurrence during their follow-up, others experience a very dismal clinical course with early and multiple tumor recurrences potentially leading to the death of patients
Summary
More than 30% of intracranial CNS tumors represent meningiomas which are considered slowly growing tumors in the majority of cases [1, 2]. To describe the biological tumor behavior, the World Health Organization (WHO) has tried to classify meningiomas by a three-tiered system based on histopathological criteria [6, 7]. In this sense, WHO grade I meningiomas are considered benign and usually do not require further treatment after surgical resection [4, 7]. Accounting for 15–20% of all meningiomas, WHO grade II meningiomas represent an intermediate group regarding risk of tumor recurrence. Even within this subgroup varying clinical courses are observed with potential occurrence of multiple recurrences. Aim of this study was to investigate DNA methylation profiles in WHO grade II meningiomas
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