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High grade serous ovarian cancer organoids as models of chromosomal instability

ABSTRACT: High-grade serous ovarian carcinoma (HGSOC) is the most genomically complex cancer, characterised by ubiquitous TP53 mutation, profound structural variation and heterogeneity. Multiple mutational processes driving chromosomal instability can be distinguished by specific copy number signatures. To develop clinically relevant models of these mutational processes we derived 15 continuous HGSOC patient-derived organoids (PDOs) and provide detailed transcriptomic and genomic profiles using shallow whole genome sequencing single cell and bulk analysis. We show that PDOs comprise communities of different clonal populations and represent models of CCNE1 amplification, chromothripsis, tandem-duplicator phenotype and whole genome duplication. PDOs can also be used as exploratory tools to study transcriptional effects of copy number alterations as well as compound-sensitivity tests. In summary, HGSOC PDO cultures provide a genomic tool for studies of specific mutational processes and precision therapeutics.

ORGANISM(S): Homo sapiens

PROVIDER: GSE208216 | GEO | 2022/07/17

REPOSITORIES: GEO

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