Large-scale sequencing projects and sequencing of patient samples can reveal mutations or polymorphisms in many genes, but the functional consequences are not always apparent especially for single amino acid substitutions. My research project focussed on addressing the discrepancy between the amount of sequenced gene variants and the knowledge about their functionality in development and disease. We developed Drosophila genetic assays for rapid, inexpensive functionalization of human PTEN variants with unknown significance (VUS) in order to learn if individual mutations play a role in development of disease. We assayed the ability of PTEN variants to suppress phenotypes observed when the oncogenic phosphoinositide 3-kinase (PI3K) signalling pathway is activated in the developing Drosophila wing. Our assay was validated with a few previously studied variants followed by characterizing 100+ human PTEN VUS. Ultimately, knowing which PTEN variants are non-functional or functional is crucial for targeted therapeutic and personalized treatment of PI3K-dependent diseases and cancers.
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Thesis advisor: Verheyen, Esther
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