Meta Rahmina, Boldt Henning B, Kristensen Bjarne W, Sahm Felix, Sjursen Wenche, Torp Sverre H
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
Department of Pathology, Odense University Hospital, 5000 Odense, Denmark.
Cancers (Basel). 2021 Mar 12;13(6):1262. doi: 10.3390/cancers13061262.
: Due to the solely subjective histopathological assessment, the WHO 2016 classification of human meningiomas is subject to interobserver variation. Consequently, the need for more reliable and objective markers are highly needed. The aim of this pilot study was to apply genome-wide DNA methylation analysis on a series of atypical meningiomas to evaluate the practical utility of this approach, examine whether prognostic subclasses are achieved and investigate whether there is an association between the methylation subclasses with poor prognosis and time to recurrence. mutation analyses were also performed to explore the prognostic value of such mutations in these atypical meningiomas. : Twenty intracranial WHO grade II atypical meningiomas from adult patients were included. They consisted of 10 cases with recurrence (group I), and 10 cases without recurrence (). The formalin-fixed and paraffin-embedded tissues underwent standardized genome-wide DNA methylation analysis, and the profiles were matched with the reference library and tumor classifier from Heidelberg. somatic mutation analyses were performed using the CNSv1panel from Düsseldorf. : Eighteen out of 20 cases matched to the meningioma class using the common brain tumor classifier (v11b4). Four of these cases matched to a methylation subclass related to a prognostic subgroup based on a cut-off of 0.9. mutations were detected in 55% of cases across both groups, and the most prominent copy number alterations were chromosomal losses of 22q, 1p and 14q. No significant mutations were identified. : Genome-wide DNA methylation profiling represents a useful tool in the diagnostics of meningiomas, however, methodological adjustments need to be addressed.
由于仅依靠主观的组织病理学评估，世界卫生组织2016年人类脑膜瘤分类存在观察者间差异。因此，迫切需要更可靠、客观的标志物。本初步研究的目的是对一系列非典型脑膜瘤进行全基因组DNA甲基化分析，以评估该方法的实际效用，检查是否能实现预后亚类划分，并研究甲基化亚类与预后不良及复发时间之间是否存在关联。还进行了突变分析，以探索这些非典型脑膜瘤中此类突变的预后价值。纳入了20例成年患者的颅内世界卫生组织II级非典型脑膜瘤。其中包括10例复发患者（第一组）和10例未复发患者。对福尔马林固定、石蜡包埋的组织进行标准化全基因组DNA甲基化分析，并将图谱与来自海德堡的参考文库和肿瘤分类器进行匹配。使用来自杜塞尔多夫的CNSv1panel进行体细胞突变分析。20例中有18例使用常见脑肿瘤分类器（v11b4）与脑膜瘤类别匹配。其中4例根据0.9的临界值与一个与预后亚组相关的甲基化亚类匹配。两组中55%的病例检测到突变，最显著的拷贝数改变是22q、1p和14q的染色体缺失。未发现显著的 突变。全基因组DNA甲基化谱分析是脑膜瘤诊断中的一种有用工具，然而，需要解决方法学调整问题。
