小柯机器人

加拿大多伦多大学Gelareh Zadeh团队建立临床上适用的脑膜瘤综合分子分类法。这一研究成果于2021年8月25日在线发表在国际学术期刊《自然》上。

研究人员将DNA体细胞拷贝数畸变、DNA体细胞点突变、DNA甲基化和信使RNA丰度结合在一起进行统一分析，介绍了脑膜瘤的四个一致的分子组别。与现有的分类方案相比，这些分子组别更准确地预测了临床结果。每个分子组别都显示出独特的原型生物学特征（免疫源性、良性NF2野生型、高代谢性和增殖性），为治疗方案提供依据。蛋白质基因组学特征加强了新定义的分子组别的稳健性，并发现了高度丰富和组内特异的蛋白质目标，研究人员用免疫组织化学进行了验证。单细胞RNA测序显示了脑膜瘤的个体间差异，以及肿瘤细胞内在表达程序的变化，这反映了所确定分子组别的生物学特性。

据了解，脑膜瘤是成人中最常见的原发性颅内肿瘤。由于没有有效的药物疗法，有症状的患者一般采用手术治疗。世界卫生组织的肿瘤组织病理学分级和手术时的切除范围（辛普森分级）与疾病的复发有关；然而，它们并不能准确反映所有脑膜瘤的临床表现。当前需要对脑膜瘤进行分子分类，从而可靠地反映肿瘤行为并为治疗提供信息。

附：英文原文

Title: A clinically applicable integrative molecular classification of meningiomas

Author: Nassiri, Farshad, Liu, Jeff, Patil, Vikas, Mamatjan, Yasin, Wang, Justin Z., Hugh-White, Rupert, Macklin, Andrew M., Khan, Shahbaz, Singh, Olivia, Karimi, Shirin, Corona, Rosario I., Liu, Lydia Y., Chen, Caroline Y., Chakravarthy, Ankur, Wei, Qingxia, Mehani, Bharati, Suppiah, Suganth, Gao, Andrew, Workewych, Adriana M., Tabatabai, Ghazaleh, Boutros, Paul C., Bader, Gary D., de Carvalho, Daniel D., Kislinger, Thomas, Aldape, Kenneth, Zadeh, Gelareh

Issue&Volume: 2021-08-25

Abstract: Meningiomas are the most common primary intracranial tumour in adults1. Patients with symptoms are generally treated with surgery as there are no effective medical therapies. The World Health Organization histopathological grade of the tumour and the extent of resection at surgery (Simpson grade) are associated with the recurrence of disease; however, they do not accurately reflect the clinical behaviour of all meningiomas2. Molecular classifications of meningioma that reliably reflect tumour behaviour and inform on therapies are required. Here we introduce four consensus molecular groups of meningioma by combining DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation and messenger RNA abundance in a unified analysis. These molecular groups more accurately predicted clinical outcomes compared with existing classification schemes. Each molecular group showed distinctive and prototypical biology (immunogenic, benign NF2 wild-type, hypermetabolic and proliferative) that informed therapeutic options. Proteogenomic characterization reinforced the robustness of the newly defined molecular groups and uncovered highly abundant and group-specific protein targets that we validated using immunohistochemistry. Single-cell RNA sequencing revealed inter-individual variations in meningioma as well as variations in intrinsic expression programs in neoplastic cells that mirrored the biology of the molecular groups identified.

DOI: 10.1038/s41586-021-03850-3

Source: https://www.nature.com/articles/s41586-021-03850-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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