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. Overall design: We examined the global transcriptional effects of PIK3CA variants in our model system via RNA-Sequencing on end-stage tumors driven by the variants.