Chen Andrea, Hart Shannon Louise, Lannon Melissa, Hawkins Cynthia, Reddy Kesava K V, Lu Jian-Qiang
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Department of Surgery/Neurosurgery, McMaster University, Hamilton, Ontario, Canada.
J Neuropathol Exp Neurol. 2025 Apr 1;84(4):329-336. doi: 10.1093/jnen/nlae135.
Rubinstein-Taybi syndrome (RTS) is a congenital disorder with characteristic clinical manifestations. In the vast majority of cases, it is caused by mutations of the gene encoding the transcriptional co-activator cAMP-response element binding protein (CBP)-binding protein (CREBBP). It has been thought to be a tumor predisposition syndrome as RTS patients have an increased risk of developing tumors including meningiomas. However, RTS-associated meningiomas are rarely reported. We report a unique RTS-associated meningioma in which an oncogenic CREBBP mutation is identified. We also comprehensively review the reported RTS-associated meningiomas, from epidemiology and pathogenesis to clinicopathological characteristics and treatment. All RTS patients with meningiomas are female and have the exclusive mutations of CREBBP. In population-based studies RTS-associated meningiomas seem to develop at younger ages. Their pathogenesis may be driven by the CREBBP/CBP alterations resulting in aberrant signal transduction in the CBP-mediated signaling pathways. Meningiomas in RTS patients have common clinicopathological characteristics including comorbidity with other tumors, radiologically intra-osseous growth, and uncommon histopathology such as ossifying and secretory features. Given the genetic nature and rarity of RTS-associated meningiomas, further investigation of their characteristics may define molecular targets for improved therapeutic options for RTS patients.
鲁宾斯坦-泰比综合征（RTS）是一种具有特征性临床表现的先天性疾病。在绝大多数情况下，它是由编码转录共激活因子环磷酸腺苷反应元件结合蛋白（CBP）结合蛋白（CREBBP）的基因突变引起的。由于RTS患者发生包括脑膜瘤在内的肿瘤的风险增加，它一直被认为是一种肿瘤易感综合征。然而，RTS相关的脑膜瘤很少有报道。我们报告了一例独特的RTS相关脑膜瘤，其中鉴定出一种致癌性CREBBP突变。我们还全面回顾了已报道的RTS相关脑膜瘤，从流行病学和发病机制到临床病理特征及治疗。所有患有脑膜瘤的RTS患者均为女性，且具有CREBBP的排他性突变。在基于人群的研究中，RTS相关脑膜瘤似乎在较年轻的年龄发病。其发病机制可能是由CREBBP/CBP改变导致CBP介导的信号通路中异常信号转导所驱动。RTS患者的脑膜瘤具有常见的临床病理特征，包括与其他肿瘤合并存在、放射学上的骨内生长以及罕见的组织病理学特征，如骨化和分泌特征。鉴于RTS相关脑膜瘤的遗传性质和罕见性，对其特征的进一步研究可能会确定分子靶点，以改善RTS患者的治疗选择。
