The repertoire of serous ovarian cancer non-genetic heterogeneity (Hu et al., 2020), published in Cancer Cell, asks how much of the variability inside a serous ovarian tumor comes from cells switching between states rather than from mutations. That kind of variability helps tumors survive stress, but it is hard to measure, because genetic differences between cells blur it. The authors' answer was to start from the normal fallopian tube epithelium, where the disease is thought to begin, and use its cell states as a reference.
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Key Findings
- Normal tube epithelium already holds distinct cell states. Sequencing about 6,000 epithelial cells, mostly from women without ovarian cancer, the authors identified six subtypes of fallopian tube epithelial cells.
- Tumors carry a mix of those states. Using each subtype's gene signature to read tumor expression data, they found substantial variability within individual tumors.
- The mix tracks survival. Grouping about 1,700 tumors by their subtype makeup separated patients by survival, a basis for more accurate prognosis.
The charts below come from the authors' deposited matrix of 1,857 cells from 5 donors. They show the epithelial cell states in that data, and that the programs defining them hold up in an independent atlas.
The Dataset
- Cells: 1,857 benign fallopian tube epithelial cells, sequenced full length (Smart-seq2), one library per cell.
- Donors: 5 donors across 6 plates.
- Source: the authors' GEO count matrix (GSE139079).
Paper: Hu Z, Artibani M, Alsaadi A, et al. The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells. Cancer Cell 37, 226–242 (2020). doi:10.1016/j.ccell.2020.01.003