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Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma

Author

Listed:
  • Clare A. Rebbeck

    (University of Cambridge)

  • Jian Xian

    (University of Cambridge)

  • Susanne Bornelöv

    (University of Cambridge)

  • Joseph Geradts

    (East Carolina University Brody School of Medicine)

  • Amy Hobeika

    (Duke University Medical Center)

  • Heather Geiger

    (New York Genome Center)

  • Jose Franco Alvarez

    (University of Cambridge)

  • Elena Rozhkova

    (Boston University School of Medicine)

  • Ashley Nicholls

    (University of Cambridge)

  • Nicolas Robine

    (New York Genome Center)

  • Herbert K. Lyerly

    (Duke University Medical Center)

  • Gregory J. Hannon

    (University of Cambridge)

Abstract

Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive ductal carcinoma (IDC) is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients, and even within patients. Here we show gene expression analysis from > 2,000 individually micro-dissected ductal lesions representing 145 patients. Combining all samples into one continuous trajectory we show there is a progressive loss in basal layer integrity heading towards IDC, coupled with two epithelial to mesenchymal transitions, one early and a second coinciding with the convergence of DCIS and IDC expression profiles. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.

Suggested Citation

  • Clare A. Rebbeck & Jian Xian & Susanne Bornelöv & Joseph Geradts & Amy Hobeika & Heather Geiger & Jose Franco Alvarez & Elena Rozhkova & Ashley Nicholls & Nicolas Robine & Herbert K. Lyerly & Gregory , 2022. "Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30573-4
    DOI: 10.1038/s41467-022-30573-4
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    1. Elvin Wagenblast & Mar Soto & Sara Gutiérrez-Ángel & Christina A. Hartl & Annika L. Gable & Ashley R. Maceli & Nicolas Erard & Alissa M. Williams & Sun Y. Kim & Steffen Dickopf & J. Chuck Harrell & An, 2015. "A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis," Nature, Nature, vol. 520(7547), pages 358-362, April.
    2. Bhupinder Pal & Yunshun Chen & François Vaillant & Paul Jamieson & Lavinia Gordon & Anne C. Rios & Stephen Wilcox & Naiyang Fu & Kevin He Liu & Felicity C. Jackling & Melissa J. Davis & Geoffrey J. Li, 2017. "Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
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    Cited by:

    1. Xinyi Zhang & Saradha Venkatachalapathy & Daniel Paysan & Paulina Schaerer & Claudio Tripodo & Caroline Uhler & G. V. Shivashankar, 2024. "Unsupervised representation learning of chromatin images identifies changes in cell state and tissue organization in DCIS," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Amanda Janesick & Robert Shelansky & Andrew D. Gottscho & Florian Wagner & Stephen R. Williams & Morgane Rouault & Ghezal Beliakoff & Carolyn A. Morrison & Michelli F. Oliveira & Jordan T. Sicherman &, 2023. "High resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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