Deciphering the longitudinal trajectories of glioblastoma ecosystems by integrative single-cell genomics

The evolution of isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) after standard-of-care therapy remains poorly understood. Here we analyzed matched primary and recurrent GBMs from 59 patients using single-nucleus RNA sequencing and bulk DNA sequencing, assessing the longitudinal evolution of the GBM ecosystem across layers of cellular and molecular heterogeneity. The most consistent change was a lower malignant cell fraction at recurrence and a reciprocal increase in glial and neuronal cell types in the tumor microenvironment (TME). The predominant malignant cell state differed between most matched pairs, but no states were exclusive or highly enriched in either time point, nor was there a…

• CC
  Conquer Cancer Foundation
• FN
  Fonds National de la Recherche Luxembourg

  Award: C20/BM/14646004/GLASSLUX
• CF
  Council for Higher Education
• S
  Servier
• NI
  National Institutes of Health

  Awards: P30CA240139, R21NS114873, P30CA013696, CA006516, R21CA256575, R01CA237208, P30CA034196, P50CA165962, P30 CA006516
• UO
  University of Texas MD Anderson Cancer Center
• JS
  Japan Society for the Promotion of Science

  Award: P30CA013696
• NC
  National Cancer Institute

  Awards: R01CA239721, R01CA276765, P30CA034196, P50CA165962, P30 CA006516, P30CA240139, CA006516, P30CA013696