TY - JOUR T1 - Tumor evolution of glioma intrinsic gene expression subtype associates with immunological changes in the microenvironment JF - bioRxiv DO - 10.1101/052076 SP - 052076 AU - Qianghu Wang AU - Xin Hu AU - Florian Muller AU - Hoon Kim AU - Massimo Squatrito AU - Tom Mikkelsen AU - Lisa Scarpace AU - Floris Barthel AU - Yu-Hsi Lin AU - Nikunj Satani AU - Emmanuel Martinez-Ledesma AU - Edward Chang AU - Adriana Olar AU - Baoli Hu AU - Ana C. deCarvalho AU - Eskil Eskilsson AU - Siyuan Zheng AU - Amy B. Heimberger AU - Erik P. Sulman AU - Do-Hyun Nam AU - Roel G.W. Verhaak Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/05/08/052076.abstract N2 - 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. ER -