Project description:Glioblastoma (GBM) is the most frequent and most aggressive form of diffuse glioma. The prognosis is very poor, with a median overall survival of 15 months after maximum safe resection and radiochemotherapy.GBM is one of the most genetically unstable cancers. It is characterized by numerous chromosome (chr) copy number alterations (CNA), such as chr 7 gain, chr 9p loss, and chr 10 loss, along with CDKN2A homozygous deletion (chr 9p21) and EGFR amplification (chr 7p11).Chromosome instability (CIN) may be the cause or the consequence of GBM development. In high-grade diffuse gliomas (HGG), CIN may initiate tumorigenesis. To identify recurrent genomic abnormalities in IDH WT glioblastomas, SNP arrays (Illumina 850K CytoSNP) were analyzed for 123 IDH WT GBM cases.
Project description:This work lays the foundation for the intratumoral immune infiltrates of glioma patients analyzed at a single cell level with the dual purpose of establishing the relevance of a new mouse model of GBM with regard to the patient disease. The aim of this study was to determine the level of concordance between the spontaneous and implanted Qk/trp53/Pten (QPP) triple-knockout mouse GBM model and human glioma samples in regard to their immune infiltrates.We analyzed a cohort of fifteen spontaneous QPP mice, nine implanted QPP mice and 10 glioma patients histopathologically. Furthermore, we analyzed three spontaneous QPP mice, thee implanted QPP mice, and 10 glioma patients by single cell RNA sequencing. We found that the QPP model recapitulates human GBM regarding the major immune components including a predominantly myeloid cell population of monocytes, macrophages, and resting dendritic cells, with minor populations of T, B, and NK cells. In addition, the complexity of the myeloid cell populations is preserved between the QPP model and the human disease.