GSE124766 Preservation of stemness in high-grade serous ovarian cancer organoids requires low Wnt environment

Contributors : Mirjana Kessler ; Karen Hoffmann ; Hans Mollenkopf ; Thomas Meyer ; Hilmar BergerSeries Type : Expression profiling by arrayOrganism : Homo sapiensHigh-grade serous ovarian cancer (HGSOC) creates a unique clinical challenge due to late detection, limited therapeutic options and wide-spread resistance to chemotherapy, all of which lead to very low survival rates. It is now widely recognized that this cancer emerges as metastasis from the fallopian tube and the lack of suitable in vitro disease models poses a major obstacle for efforts to improve our understanding of this deadly disease. We used organoids of healthy human FT epithelium as a model for stepwise genetic modification towards malignancy, using shRNA-mediated knockdown (KD) of three major HGSOC driver genes: P53, PTEN and Retinoblastoma (RB). Moreover, we successfully established patient-derived HGSOC organoids from solid tumor deposits. After combinatorial screening approach of different media compositions we have established 15 organoid lines which depend on the absence of exogenous Wnt3a in the medium. We could show that those cultures closely resemble the parental tumor tissue and express hallmarks of HGSOC phenotype as revealed by histology and global gene expression profiles of the matching organoid and tissue samples. Expression and sequencing analysis revealed that all samples were characterized by p53 mutation and/or aberrant p53 expression. Interestingly, the addition of Wnt agonists to cance...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

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