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- W2971222015 abstract "Abstract Resistant tumours are thought to arise from the action of Darwinian selection on genetically heterogenous cancer cell populations. However, simple clonal selection is inadequate to describe the late relapses often characterising luminal breast cancers treated with endocrine therapy (ET), suggesting a more complex interplay between genetic and non-genetic factors. Here, we dissect the contributions of clonal genetic diversity and transcriptional plasticity during the early and late phases of ET at single-cell resolution. Using single-cell RNA-sequencing and imaging we disentangle the transcriptional variability of plastic cells and define a rare subpopulation of pre-adapted (PA) cells which undergoes further transcriptomic reprogramming and copy number changes to acquire full resistance. We find evidence for sub-clonal expression of a PA signature in primary tumours and for dominant expression in clustered circulating tumour cells. We propose a multi-step model for ET resistance development and advocate the use of stage-specific biomarkers." @default.
- W2971222015 created "2019-09-05" @default.
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- W2971222015 date "2019-09-02" @default.
- W2971222015 modified "2023-10-18" @default.
- W2971222015 title "Single-cell transcriptomics reveals multi-step adaptations to endocrine therapy" @default.
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- W2971222015 doi "https://doi.org/10.1038/s41467-019-11721-9" @default.
- W2971222015 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6718416" @default.
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