神外前沿訊，近日，CELL雜志發表題為《Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective》的研究文章。
腦膠質母細胞瘤(GBM)的治療失敗，通常歸因於瘤內異質性和腫瘤演變。
在手術切除過程中，研究人員使用3D神經導航來獲取通過3D空間坐標映射的代表整個腫瘤的樣本。綜合組織和單細胞分析揭示了基因組、表觀基因組和微環境腫瘤內異質性的來源及其空間模式。通過區分腫瘤范圍內的分子特征和具有區域特異性的分子特征，研究人員推斷了GBM的演化軌跡，從神經發育譜系起源和啟動事件，如染色體裂解，到遺傳亞克隆的出現，以及在核心、外圍和對比度增強區域的差異腫瘤和微環境程序的空間限制激活。
總之，這一工作從3D全腫瘤的角度描述了GBM的演化和異質性，強調了可能規避異質性相關失敗的潛在治療靶點，並建立了一個交互式平臺，能夠360°可視化和分析用戶選擇的基因、程序和其他特征在整個GBM腫瘤中的3D空間模式。
原文
Title: Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective
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