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The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC. Surveying the transcriptomes of ∼6,000 FTE cells, predominantly from non-ovarian cancer patients, identified 6 FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH. Importantly, NGH-based stratification of ∼1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.

Original publication




Journal article


Cancer cell

Publication Date





226 - 242.e7


Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford OX3 9DU, UK; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.


Fallopian Tubes, Epithelium, Epithelial Cells, Humans, Cystadenocarcinoma, Serous, Ovarian Neoplasms, Fallopian Tube Neoplasms, Gene Expression Regulation, Neoplastic, Genetic Heterogeneity, Female