美国加州大学Joseph F. Costello和美国西北大学Feng Yue共同合作，近期取得重要工作进展。他们研究提出了从三维全肿瘤视角，观察胶质母细胞瘤的演化和异质性的方法。相关研究成果2024年1月18日在线发表于《细胞》杂志上。

据介绍，致死性脑肿瘤胶质母细胞瘤（GBM）的治疗失败归因于瘤内异质性和肿瘤的演变。

在手术切除过程中，研究人员使用3D神经导航来获取通过3D空间坐标映射的代表整个肿瘤的样本。综合组织和单细胞分析揭示了基因组、表观基因组和微环境肿瘤内异质性的来源及其空间模式。通过区分肿瘤范围内的分子特征和具有区域特异性的分子特征，研究人员推断了GBM的演化轨迹，从神经发育谱系起源和启动事件，如染色体裂解，到遗传亚克隆的出现，以及在核心、外围和对比度增强区域的差异肿瘤和微环境程序的空间限制激活。。

总之，这一工作从3D全肿瘤的角度描述了GBM的演化和异质性，强调了可能规避异质性相关失败的潜在治疗靶点，并建立了一个交互式平台，能够360°可视化和分析用户选择的基因、程序和其他特征在整个GBM肿瘤中的3D空间模式。

附：英文原文

Title: Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective

Author: Radhika Mathur, Qixuan Wang, Patrick G. Schupp, Ana Nikolic, Stephanie Hilz, Chibo Hong, Nadia R. Grishanina, Darwin Kwok, Nicholas O. Stevers, Qiushi Jin, Mark W. Youngblood, Lena Ann Stasiak, Ye Hou, Juan Wang, Takafumi N. Yamaguchi, Marisa Lafontaine, Anny Shai, Ivan V. Smirnov, David A. Solomon, Susan M. Chang, Shawn L. Hervey-Jumper, Mitchel S. Berger, Janine M. Lupo, Hideho Okada, Joanna J. Phillips, Paul C. Boutros, Marco Gallo, Michael C. Oldham, Feng Yue, Joseph F. Costello

Issue&Volume: 2024/01/18

Abstract: Treatment failure for the lethal brain tumor glioblastoma (GBM) is attributed to intratumoralheterogeneity and tumor evolution. We utilized 3D neuronavigation during surgicalresection to acquire samples representing the whole tumor mapped by 3D spatial coordinates.Integrative tissue and single-cell analysis revealed sources of genomic, epigenomic,and microenvironmental intratumoral heterogeneity and their spatial patterning. Bydistinguishing tumor-wide molecular features from those with regional specificity,we inferred GBM evolutionary trajectories from neurodevelopmental lineage originsand initiating events such as chromothripsis to emergence of genetic subclones andspatially restricted activation of differential tumor and microenvironmental programsin the core, periphery, and contrast-enhancing regions. Our work depicts GBM evolutionand heterogeneity from a 3D whole-tumor perspective, highlights potential therapeutictargets that might circumvent heterogeneity-related failures, and establishes an interactiveplatform enabling 360° visualization and analysis of 3D spatial patterns for user-selectedgenes, programs, and other features across whole GBM tumors.

DOI: 10.1016/j.cell.2023.12.013

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01345-4