RT Journal Article SR Electronic T1 Tumor evolution of glioma intrinsic gene expression subtype associates with immunological changes in the microenvironment JF bioRxiv FD Cold Spring Harbor Laboratory SP 052076 DO 10.1101/052076 A1 Qianghu Wang A1 Xin Hu A1 Florian Muller A1 Hoon Kim A1 Massimo Squatrito A1 Tom Mikkelsen A1 Lisa Scarpace A1 Floris Barthel A1 Yu-Hsi Lin A1 Nikunj Satani A1 Emmanuel Martinez-Ledesma A1 Edward Chang A1 Adriana Olar A1 Baoli Hu A1 Ana C. deCarvalho A1 Eskil Eskilsson A1 Siyuan Zheng A1 Amy B. Heimberger A1 Erik P. Sulman A1 Do-Hyun Nam A1 Roel G.W. Verhaak YR 2016 UL http://biorxiv.org/content/early/2016/05/08/052076.abstract AB We leveraged IDH wild type glioblastomas (GBM) and derivative neurosphere models to define the tumor-intrinsic mRNA transcription phenotype. We found that intratumoral heterogeneity is reflected in the transcriptome and associated with increased tumor microenvironment presence. We performed in silico cell sorting to demonstrate that M2 macrophages/microglia are the most frequent type of immune cells in the glioma microenvironment, followed by CD4+ T lymphocytes. Longitudinal transcriptome analysis of 124 pairs of primary and recurrent glioma pairs showed expression subtype is retained in 53% of cases with no proneural to mesenchymal transition being apparent. Inference of the tumor microenvironment through gene signatures revealed a decrease in invading monocytes but a subtype dependent increase in M2 macrophages/microglia cells after disease recurrence. Our longitudinal expression dataset can be accessed at http://ackbar.cnio.es:3838/RecuR/. Our study provides a comprehensive transcriptional and cellular landscape of IDH wild type GBM during treatment modulated tumor evolution.