Project description:We measured gene expression in single-cell RNA sequencing samples from patients with high-grade serous ovarian cancer (HGSOC), for a study on improving HGSOC subtype definition by taking into account varying cell type proportions within tumors.
Project description:Purpose: Characterization of the gene expression profile and TCR profile of CD8+ TILs (TRM and re-circulating) from HGSOC to understand the immunogenicity of ovarian cancer
Project description:Purpose: Characterization of the gene expression profile and TCR profile of CD8+ TILs (TRM and re-circulating) from HGSOC to understand the immunogenicity of ovarian cancer
Project description:Tumor cells were isolated from solid tumors or ascites from HGSOC patients and enriched for EpCAM expression by antibody magnetic beads (affinity)-based methods and large RNAs (> 200 nt) sequenced (50 bp paired ends) after rRNA depletion (RiboZero). Expression differences between patients with miliary and non-miliary peritoneal tumor spreading were used for a search for new targeted therapies and for biological annotion.
Project description:High-grade serous ovarian carcinoma (HGSOC) is the most genomically complex cancer, characterized by ubiquitous TP53 mutation, profound chromosomal instability and heterogeneity. The mutational processes driving chromosomal instability in HGSOC 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 characterized them using bulk transcriptomic, bulk genomic, single cell genomic, and drug sensitivity assays. We show that HGSOC PDOs comprise communities of different clonal populations and represent models of different causes of chromosomal instability including homologous recombination deficiency, chromothripsis, tandem-duplicator phenotype and whole genome duplication. We also show that these PDOs can 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 validated genomic models for studies of specific mutational processes and precision therapeutics.
