DNA Methylation Associates With Clinical Courses of Atypical Meningiomas: A Matched Case–Control Study

Frontiers in Oncology

Felix Sahm¹  Alice Senta Ryba²  Matthias Millesi²  Stefan Wolfsberger²  Karl Roessler²  Matthias Preusser³  Gerwin Heller³  Anna Sophie Berghoff³  Erwin Tomasich³  Thomas Roetzer⁶  Johannes A. Hainfellner⁶ 

[1] Clinical Cooperation Unit (CCU), German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany;Comprehensive Cancer Center, Central Nervous System Unit, Medical University of Vienna, Vienna, Austria;Department of Internal Medicine I/Oncology, Medical University of Vienna, Vienna, Austria;Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany;Department of Neurosurgery, Medical University of Vienna, Vienna, Austria;Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria;

关键词: meningioma;    atypical;    DNA methylation;    Wnt pathway;    prognosis;   

DOI  :  10.3389/fonc.2022.811729

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown