Journal article

A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast

Bhupinder Pal, Yunshun Chen, Francois Vaillant, Bianca D Capaldo, Rachel Joyce, Xiaoyu Song, Vanessa L Bryant, Jocelyn S Penington, Leon Di Stefano, Nina Tubau Ribera, Stephen Wilcox, Gregory B Mann, Anthony T Papenfuss, Geoffrey J Lindeman, Gordon K Smyth, Jane E Visvader

EMBO JOURNAL | WILEY | Published : 2021

Abstract

To examine global changes in breast heterogeneity across different states, we determined the single-cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1+/- tissue, the major breast cancer subtypes, and pairs of tumors and involved lymph nodes. Elucidation of the normal breast microenvironment revealed striking changes in the stroma of post-menopausal women. Single-cell profiling of 34 treatment-naive primary tumors, including estrogen receptor (ER)+ , HER2+ , and triple-negative breast cancers, revealed comparable diversity among cancer cells and a discrete subset of cycling cells. The transcriptomes of preneoplastic BRCA1+/- tissue versus tumors highlighted..

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Grants

Awarded by National Breast Cancer Foundation (NBCF)


Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by NHMRC Fellowships


Funding Acknowledgements

We are grateful to S Nutt, D Gray, and L Whitehead for discussions, H.K. Liu and E Surgenor for expert assistance, the Imaging and FACS facilities at WEHI, Leanne Taylor and colleagues from the Royal Melbourne Hospital Tissue Bank and the Victorian Cancer Biobank, Heather Thorne and all contributors to the Kathleen Cuningham Foundation Consortium for research into Familial Breast cancer (kConFab). This work was supported by the National Breast Cancer Foundation (NBCF, IIRS-20-022), Australian National Health and Medical Research Council (NHMRC) grants (#1054618, 1100807, 1113133, 1153049); NHMRC IRIISS; the Victorian State Government Operational Infrastructure Support; the Australian Cancer Research Foundation and the Ian Potter Foundation. G.J.L., G.K.S. and J.E.V. were supported by NHMRC Fellowships (G.J.L. #1078730 and 1175960; G.K.S. #1058892; J.E.V. #1037230 and 1102742).