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

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2024-01-18 DOI:10.1016/j.cell.2023.12.013

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

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引用次数: 0

Abstract

Treatment failure for the lethal brain tumor glioblastoma (GBM) is attributed to intratumoral heterogeneity and tumor evolution. We utilized 3D neuronavigation during surgical resection 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. By distinguishing tumor-wide molecular features from those with regional specificity, we inferred GBM evolutionary trajectories from neurodevelopmental lineage origins and initiating events such as chromothripsis to emergence of genetic subclones and spatially restricted activation of differential tumor and microenvironmental programs in the core, periphery, and contrast-enhancing regions. Our work depicts GBM evolution and heterogeneity from a 3D whole-tumor perspective, highlights potential therapeutic targets that might circumvent heterogeneity-related failures, and establishes an interactive platform enabling 360° visualization and analysis of 3D spatial patterns for user-selected genes, programs, and other features across whole GBM tumors.

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从三维全肿瘤角度看胶质母细胞瘤的演变和异质性。

致命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演变。我们在手术切除过程中利用三维神经导航技术获取了代表三维空间坐标映射的整个肿瘤的样本。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瘤内异质性的来源及其空间模式。通过区分整个肿瘤的分子特征和具有区域特异性的分子特征，我们推断出了 GBM 的进化轨迹，从神经发育系起源和染色体三体等启动事件，到基因亚克隆的出现，以及在核心、外围和对比度增强区域不同肿瘤和微环境程序的空间限制性激活。我们的研究从三维全肿瘤的角度描绘了 GBM 的进化和异质性，突出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，可对用户选择的基因、程序和整个 GBM 肿瘤的其他特征进行 360° 可视化和三维空间模式分析。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.