Transcriptome analysis of human glioblastoma tumor cells driven by PIK3CA mutation variants

The RTK/RAS/PI3K pathway is a key driver of tumorigenesis across all cancers, with 90% of Glioblastoma (GBM) tumors exhibiting alterations in this pathway. Among the specific genes in this pathway mutations in PI3K’s catalytic subunit, PIK3CA, are found in 11% of GBM tumors. Sequencing of GBM samples has revealed several known hotspot mutations that drive tumorigenesis in several cancers (E545K, H1047R), as well as a series of 63 in frame mutations (as indexed in COSMIC) that remain largely unclassified. Cells from patient-derived primary GBM cell lines were lentivirally infected with different PIK3CA mutants (or a mCherry control reporter), and implanted in mice. The resulting tumors were then profiled for gene expression. We examined the global transcriptional effects of PIK3CA variants in our model system via RNA-Sequencing on end-stage tumors driven by the variants.