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
{"title":"从三维全肿瘤角度看胶质母细胞瘤的演变和异质性。","authors":"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","doi":"10.1016/j.cell.2023.12.013","DOIUrl":null,"url":null,"abstract":"<p><p>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. 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Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective.
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.
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.
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