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- W2949081129 abstract "Abstract The PIK3CA gene, which encodes the p110α catalytic subunit of PI3-kinase (PI3K), is mutationally activated in cancer and in overgrowth disorders known as PIK3CA -related overgrowth spectrum (PROS). To determine the consequences of genetic PIK3CA activation in a developmental context of relevance to both PROS and cancer, we engineered isogenic human induced pluripotent stem cells (iPSCs) with heterozygous or homozygous knock-in of PIK3CA H1047R . While heterozygous iPSCs remained largely similar to wild-type cells, homozygosity for PIK3CA H1047R caused widespread, cancer-like transcriptional remodeling, partial loss of epithelial morphology, upregulation of stemness markers and impaired differentiation to all three germ layers in vitro and in vivo . Genetic analysis of PIK3CA -associated cancers revealed that 64 % had multiple oncogenic PIK3CA copies (39 %) or additional PI3K signaling pathway-activating “hits” (25 %). This contrasts with the prevailing view that PIK3CA mutations occur heterozygously in cancer. Our findings suggest that a PI3K activity threshold determines pathological consequences of oncogenic PIK3CA activation and provide the first insight into the specific role of this pathway in human pluripotent stem cells." @default.
- W2949081129 created "2019-06-27" @default.
- W2949081129 creator A5023399910 @default.
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- W2949081129 date "2018-12-13" @default.
- W2949081129 modified "2023-09-23" @default.
- W2949081129 title "Oncogenic <i>PIK3CA</i> promotes cellular stemness in an allele dose-dependent manner" @default.
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- W2949081129 doi "https://doi.org/10.1101/495093" @default.
- W2949081129 hasPublicationYear "2018" @default.
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