Umbach Gray, Tran Edwina B, Eaton Charlotte D, Choudhury Abrar, Morshed Ramin, Villanueva-Meyer Javier E, Theodosopoulos Philip V, Magill Stephen T, McDermott Michael W, Raleigh David R, Goldschmidt Ezequiel
Department of Neurological Surgery, University of California, San Francisco, San Francisco , California , USA.
School of Medicine, University of California, San Francisco, San Francisco , California , USA.
Oper Neurosurg. 2024 Jun 1;26(6):662-668. doi: 10.1227/ons.0000000000001052. Epub 2024 Jan 8.
Meningiomas are the most common primary intracranial tumors and are among the only tumors that can form lamellar, hyperostotic bone in the tumor microenvironment. Little is known about the epidemiology or molecular features of hyperostotic meningiomas.
Using a retrospective database of 342 meningiomas treated with surgery at a single institution, we correlated clinical, tumor-related, targeted next-generation DNA sequencing (n = 39 total, 16 meningioma-induced hyperostosis [MIH]), and surgical variables with the presence of MIH using generalized linear models. Meningioma DNA methylation grouping was analyzed on a separate population of patients from the same institution with preoperative imaging studies sufficient for identification of MIH (n = 200).
MIH was significantly correlated with anterior fossa (44.3% of MIH vs 17.5% of non-MIH were in the anterior fossa P < .001, c 2 ) or skull base location (62.5% vs 38.3%, P < .001, c 2 ) and lower MIB-1 labeling index. Gross total resection was accomplished in 27.3% of tumors with MIH and 45.5% of nonhyperostotic meningiomas ( P < .05, t test). There was no association between MIH and histological World Health Organization grade ( P = .32, c 2 ). MIH was significantly more frequent in meningiomas from the Merlin-intact DNA methylation group ( P < .05). Somatic missense mutations in the WD-repeat-containing domain of the TRAF7 gene were the most common genetic alteration associated with MIH (n = 12 of 15, 80%, P < .01, c 2 ).
In this article, we show that MIH has a predilection for the anterior skull base and affected tumors are less amenable to gross total resection. We find no association between MIH and histological World Health Organization grade, but show that MIH is more common in the Merlin-intact DNA methylation group and is significantly associated with TRAF7 somatic missense mutations. These data provide a framework for future investigation of biological mechanisms underlying MIH.
脑膜瘤是最常见的原发性颅内肿瘤，也是仅有的能在肿瘤微环境中形成板层状、骨质增生性骨的肿瘤之一。关于骨质增生性脑膜瘤的流行病学或分子特征，人们知之甚少。
利用一个单一机构对342例接受手术治疗的脑膜瘤的回顾性数据库，我们使用广义线性模型将临床、肿瘤相关、靶向二代DNA测序（共39例，16例为脑膜瘤诱导的骨质增生[MIH]）及手术变量与MIH的存在进行关联分析。在同一机构的另一组患者中分析脑膜瘤DNA甲基化分组情况，这些患者术前影像学检查足以识别MIH（n = 200）。
MIH与前颅窝（MIH的44.3%位于前颅窝，而非MIH的为17.5%，P <.001，c²）或颅底位置（62.5%对38.3%，P <.001，c²）以及较低的MIB-1标记指数显著相关。MIH肿瘤的全切除率为27.3%，非骨质增生性脑膜瘤为45.5%（P <.05，t检验）。MIH与世界卫生组织组织学分级之间无关联（P =.32，c²）。MIH在Merlin完整DNA甲基化组的脑膜瘤中明显更常见（P <.05）。TRAF7基因含WD重复结构域的体细胞错义突变是与MIH相关的最常见基因改变（15例中有12例，80%，P <.01，c²）。
在本文中，我们表明MIH好发于前颅底，且受累肿瘤较难实现全切除。我们发现MIH与世界卫生组织组织学分级之间无关联，但表明MIH在Merlin完整DNA甲基化组中更常见，且与TRAF7体细胞错义突变显著相关。这些数据为未来研究MIH潜在生物学机制提供了框架。
