Dwianingsih Ery Kus, Krisnugraha Yeshua Putra, Bawono Rheza Gandi, Malueka Rusdy Ghazali
Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr Sardjito General Hospital, Sekip, Yogyakarta 55281, Indonesia.
Department of Neurology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Dr Sardjito General Hospital, Sekip, Yogyakarta 55281, Indonesia.
Biomed Rep. 2025 Jan 30;22(4):56. doi: 10.3892/br.2025.1934. eCollection 2025 Apr.
Meningioma is the most common type of primary intracranial tumor. These tumors are typically slow-growing and benign [World Health Organization (WHO) grade 1]. However, 20% of meningiomas (WHO grade 2 and 3) can be difficult to treat owing to their aggressive characteristics and higher recurrence rate, which presents a significant therapeutic challenge. Histopathological grading can yield inconsistent results due to interexaminer variability, which calls for more reliable biomarkers. Genetic and epigenetic alterations may define biological behavior and predict the prognosis of meningioma. The present review highlights the relevant genetic mutations, DNA methylation status in meningioma and their associations with relevant histomorphology, location and prognosis. Mutations in TNF receptor-associated factor 7, Krüppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog (AKT1), Smoothened frizzled-class receptor (SMO), Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and RNA polymerase II subunit A (POLR2A) were associated with a good prognosis and a low recurrence rate. By contrast, mutations in NF2, TERT promoter, SMARCB1, SMARCE1, CDKN2A/B and BAP1 are associated with poor prognosis and higher recurrence rates. DNA methylation status plays a role in diagnosis, predicting tumor recurrence and prognosis. Combining the WHO grading and molecular biomarkers may lead to better diagnosis, prognosis, and targeted therapy for meningioma.
脑膜瘤是最常见的原发性颅内肿瘤类型。这些肿瘤通常生长缓慢且为良性(世界卫生组织(WHO)1级)。然而,20%的脑膜瘤(WHO 2级和3级)因其侵袭性特征和较高的复发率而难以治疗,这带来了重大的治疗挑战。由于检查者之间的差异,组织病理学分级可能产生不一致的结果,这就需要更可靠的生物标志物。基因和表观遗传改变可能决定脑膜瘤的生物学行为并预测其预后。本综述重点介绍了脑膜瘤相关的基因突变、DNA甲基化状态及其与相关组织形态学、位置和预后的关联。肿瘤坏死因子受体相关因子7、Krüppel样因子4(KLF4)、v-Akt鼠胸腺瘤病毒癌基因同源物(AKT1)、平滑卷曲类受体(SMO)、磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α(PIK3CA)和RNA聚合酶II亚基A(POLR2A)的突变与良好的预后和低复发率相关。相比之下,NF2、端粒酶逆转录酶启动子、SMARCB1、SMARCE1、CDKN2A/B和BAP1的突变与不良预后和较高的复发率相关。DNA甲基化状态在诊断、预测肿瘤复发和预后方面发挥作用。结合WHO分级和分子生物标志物可能会为脑膜瘤带来更好的诊断、预后和靶向治疗。