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Normal breast tissues harbour rare populations of aneuploid epithelial cells

Author

Listed:
  • Yiyun Lin

    (University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

  • Junke Wang

    (University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

  • Kaile Wang

    (University of Texas MD Anderson Cancer Center)

  • Shanshan Bai

    (University of Texas MD Anderson Cancer Center)

  • Aatish Thennavan

    (University of Texas MD Anderson Cancer Center)

  • Runmin Wei

    (University of Texas MD Anderson Cancer Center)

  • Yun Yan

    (University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

  • Jianzhuo Li

    (University of Texas MD Anderson Cancer Center)

  • Heba Elgamal

    (University of Texas MD Anderson Cancer Center)

  • Emi Sei

    (University of Texas MD Anderson Cancer Center)

  • Anna Casasent

    (University of Texas MD Anderson Cancer Center)

  • Mitchell Rao

    (University of Texas MD Anderson Cancer Center)

  • Chenling Tang

    (University of Texas MD Anderson Cancer Center)

  • Asha S. Multani

    (University of Texas MD Anderson Cancer Center)

  • Jin Ma

    (University of Texas MD Anderson Cancer Center)

  • Jessica Montalvan

    (Baylor College of Medicine)

  • Chandandeep Nagi

    (Baylor College of Medicine)

  • Sebastian Winocour

    (Baylor College of Medicine)

  • Bora Lim

    (University of Texas MD Anderson Cancer Center)

  • Alastair Thompson

    (Baylor College of Medicine)

  • Nicholas Navin

    (University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center
    University of Texas MD Anderson Cancer Center)

Abstract

Aneuploid epithelial cells are common in breast cancer1,2; however, their presence in normal breast tissues is not well understood. To address this question, we applied single-cell DNA sequencing to profile copy number alterations in 83,206 epithelial cells from the breast tissues of 49 healthy women, and we applied single-cell DNA and assay for transposase-accessible chromatin sequencing co-assays to the samples of 19 women. Our data show that all women harboured rare aneuploid epithelial cells (median 3.19%) that increased with age. Many aneuploid epithelial cells (median 82.22%) in normal breast tissues underwent clonal expansions and harboured copy number alterations reminiscent of invasive breast cancers (gains of 1q; losses of 10q, 16q and 22q). Co-assay profiling showed that the aneuploid cells were mainly associated with the two luminal epithelial lineages, and spatial mapping showed that they localized in ductal and lobular structures with normal histopathology. Collectively, these data show that even healthy women have clonal expansions of rare aneuploid epithelial cells in their breast tissues.

Suggested Citation

  • Yiyun Lin & Junke Wang & Kaile Wang & Shanshan Bai & Aatish Thennavan & Runmin Wei & Yun Yan & Jianzhuo Li & Heba Elgamal & Emi Sei & Anna Casasent & Mitchell Rao & Chenling Tang & Asha S. Multani & J, 2024. "Normal breast tissues harbour rare populations of aneuploid epithelial cells," Nature, Nature, vol. 636(8043), pages 663-670, December.
    • Handle: RePEc:nat:nature:v:636:y:2024:i:8043:d:10.1038_s41586-024-08129-x
    DOI: 10.1038/s41586-024-08129-x
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