Berghaus Natalie, Hielscher Thomas, Savran Dilan, Schrimpf Daniel, Maas Sybren L N, Preusser Matthias, Weller Michael, Acker Till, Herold-Mende Christel, Wick Wolfgang, von Deimling Andreas, Sahm Felix
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
Neuro Oncol. 2025 May 15;27(4):1019-1028. doi: 10.1093/neuonc/noae239.
Meningiomas are the most common primary intracranial tumors in adults. Several studies proposed new stratification systems with a more accurate risk prediction than the WHO grading, eg, based on methylation and copy-number variations (CNVs). Yet, common shortcomings in these analyses are either a lack of stratification by sex of patients or excluding the gonosomes from CNV assessment.
Within this study, DNA methylation array data from 7424 meningioma samples as well as targeted sequencing, clinical annotations, and morphology subtyping of 796 samples were examined for differences between females and males regarding mutations, methylation classes, CNVs, and histology.
Meningiomas from females accounted for about 53% of the malignant tumors and present a loss of one X chromosome in 57% of these malignant cases. In the group of benign tumors, females comprised about 75% of the patients. Therein, a loss of one X chromosome was detected in only about 10% of the cases but was associated with a significantly worse progression-free survival.
Although genomic instability is a common feature of malignant meningiomas, particularly loss of the X chromosome in tumors of female patients in otherwise histologically and molecularly low-risk tumors confers higher risk. Hence, the gonosomal copy-number status can be leveraged for increased diagnostic accuracy.
脑膜瘤是成人最常见的原发性颅内肿瘤。多项研究提出了新的分层系统，其风险预测比世界卫生组织（WHO）分级更准确，例如基于甲基化和拷贝数变异（CNV）。然而，这些分析的常见缺点是要么缺乏按患者性别分层，要么在CNV评估中排除性染色体。
在本研究中，检查了来自7424个脑膜瘤样本的DNA甲基化阵列数据以及796个样本的靶向测序、临床注释和形态学亚型，以分析女性和男性在突变、甲基化类别、CNV和组织学方面的差异。
女性脑膜瘤约占恶性肿瘤的53%，其中57%的恶性病例存在一条X染色体缺失。在良性肿瘤组中，女性约占患者的75%。其中，仅约10%的病例检测到一条X染色体缺失，但与无进展生存期显著较差相关。
虽然基因组不稳定是恶性脑膜瘤的一个共同特征，特别是在组织学和分子学上低风险肿瘤的女性患者肿瘤中X染色体缺失会带来更高风险。因此，性染色体拷贝数状态可用于提高诊断准确性。
