Glioblastoma Evolution and Heterogeneity from a 3D Whole-tumor Perspective

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2024 Jan 19

PMID 38242087

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

Affiliations

Soon will be listed here.

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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