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Ducan Cancer Center, Baylor College of Medicinehttps://www.ebi.ac.uk/ena/browser/view/PRJNA508980Mus musculusxref:PubMed:31996845The 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. To decode which of these PIK3CA variants function as drivers of GBM, we established an in vivo complementation screening platform for GBM. Our mouse GBM model relies on in utero electroporation (IUE) and CRISPR-Cas9 mediated knockout of NF1, p53, and PTEN (termed 3xCR). Because PTEN catalyzes the reverse reaction of PIK3CA, phosphorylation of PIP2 to PIP3, we complemented loss of PTEN with overexpression of E545K or H1047R, two bona fide hot spot driver mutations of PIK3CA. Both these variants accelerated tumor associated death, demonstrating that known PIK3CA drivers can complement PTEN loss in our system. 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.ENATranscriptome, Malignant Neoplasm, 6330412C24Rik, determination, Transcriptome Profile, Laboratory, Neoplasms, Mus domesticus, Expression Profiles, mouse, Benign Neoplasm, Gene Expression Profile, p110, Gene, PI3K, Profiles, Tumor, Malignant, House Mouse, whole transcriptome, Gene Expression, p110-alpha, Benign, CWS5, House, Mus, Expression Signatures, Gene Expression Signatures, chemical analysis, Neoplasm, Mus musculus domesticus, p110alpha, Mutations., Gene Expression Signature, Expression Profile, Mice, Transcriptome Profiles, Mus musculus, Malignancy, Swiss, mice, Profile, Swiss Mouse, Benign Neoplasms, House Mice, Swiss Mice, Cancers, Signatures, domesticus, Laboratory Mice, Malignant Neoplasms, Neoplasias, MCAP, caPI3K, CLOVE, Expression Signature, Gene Expression Profiles, Transcriptomes, Mouse, Malignancies, assay, house mouse, MCM, Signature, MCMTC, Laboratory Mouse, Neoplasia, Cancer, TumorsTranscriptome, Malignant Neoplasm, 6330412C24Rik, determination, Transcriptome Profile, Laboratory, Neoplasms, Mus domesticus, Expression Profiles, mouse, Benign Neoplasm, Gene Expression Profile, p110, Gene, PI3K, Profiles, Tumor, Malignant, House Mouse, whole transcriptome, Gene Expression, p110-alpha, Benign, CWS5, House, Mus, Expression Signatures, Gene Expression Signatures, chemical analysis, Neoplasm, Mus musculus domesticus, p110alpha, Mutations., Gene Expression Signature, Expression Profile, Mice, Transcriptome Profiles, Mus musculus, Malignancy, Swiss, mice, Profile, Swiss Mouse, Benign Neoplasms, House Mice, Swiss Mice, Cancers, Signatures, domesticus, Laboratory Mice, Malignant Neoplasms, Neoplasias, MCAP, caPI3K, CLOVE, Expression Signature, Gene Expression Profiles, Transcriptomes, Mouse, Malignancies, assay, house mouse, MCM, Signature, MCMTC, Laboratory Mouse, Neoplasia, Cancer, TumorsfalseTranscriptome analysis of mouse tumors driven by PIK3CA mutation variantsTranscriptome analysis of mouse tumors driven by PIK3CA mutation variants2025-09-242019-10-11PRJNA508980GSE1235191009031996845