小柯机器人

美国加州大学David R. Raleigh、美国匹兹堡大学Jeremy N. Rich以及美国西北大学Stephen T. Magill研究团队合作揭示脑膜瘤 DNA 甲基化组识别生物学驱动因素和治疗漏洞。这一研究成果发表在2022年5月9日出版的国际学术期刊《自然—遗传学》上。

他们对 565 例脑膜瘤进行 DNA 甲基化分析，并结合遗传、转录组、生化、蛋白质组和单细胞方法来表明脑膜瘤由三个 DNA 甲基化组组成，具有不同的临床预后、生物学驱动因素和治疗漏洞。Merlin 完整脑膜瘤 (34%) 具有最佳预后，其特点是 NF2/Merlin 调节对细胞毒治疗的敏感性。免疫富集的脑膜瘤（38%）具有中等预后，并以免疫浸润、HLA 表达和淋巴管为特征。有丝分裂性脑膜瘤 (28%) 的预后最差，其特点是驱动细胞周期的趋同遗传和表观遗传机制以及对细胞毒治疗的抗性。为了将这些发现转化为临床实践，他们展示了胞质细胞周期抑制剂减弱了细胞培养物、类器官、异种移植物和患者中的脑膜瘤生长。

研究人员表示，脑膜瘤是最常见的原发性颅内肿瘤。脑膜瘤患者没有有效的药物治疗方法，新的治疗方法受到对脑膜瘤生物学认知有限的阻碍。

附：英文原文

Title: Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities

Author: Choudhury, Abrar, Magill, Stephen T., Eaton, Charlotte D., Prager, Briana C., Chen, William C., Cady, Martha A., Seo, Kyounghee, Lucas, Calixto-Hope G., Casey-Clyde, Tim J., Vasudevan, Harish N., Liu, S. John, Villanueva-Meyer, Javier E., Lam, Tai-Chung, Pu, Jenny Kan-Suen, Li, Lai-Fung, Leung, Gilberto Ka-Kit, Swaney, Danielle L., Zhang, Michael Y., Chan, Jason W., Qiu, Zhixin, Martin, Michael V., Susko, Matthew S., Braunstein, Steve E., Bush, Nancy Ann Oberheim, Schulte, Jessica D., Butowski, Nicholas, Sneed, Penny K., Berger, Mitchel S., Krogan, Nevan J., Perry, Arie, Phillips, Joanna J., Solomon, David A., Costello, Joseph F., McDermott, Michael W., Rich, Jeremy N., Raleigh, David R.

Issue&Volume: 2022-05-09

Abstract: Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities. Merlin-intact meningiomas (34%) have the best outcomes and are distinguished by NF2/Merlin regulation of susceptibility to cytotoxic therapy. Immune-enriched meningiomas (38%) have intermediate outcomes and are distinguished by immune infiltration, HLA expression and lymphatic vessels. Hypermitotic meningiomas (28%) have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. To translate these findings into clinical practice, we show cytostatic cell cycle inhibitors attenuate meningioma growth in cell culture, organoids, xenografts and patients. DNA methylation profiling of 565 meningiomas highlights three groups associated with distinct molecular, clinical and therapeutic features.

DOI: 10.1038/s41588-022-01061-8

Source: https://www.nature.com/articles/s41588-022-01061-8

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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