Publications

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

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.

Nat. Communications 2022 Jun 13;13(1):3399.

PMID: 35697697 PMCID: PMC9192778 DOI: 10.1038/s41467-022-30573-4

Authors

Other Contributors

Clare A Rebbeck # 1, Jian Xian # 2, Susanne Bornelöv 2, Joseph Geradts 3, Amy Hobeika 4, Heather Geiger 5, Jose Franco Alvarez 2, Elena Rozhkova 6, Ashley Nicholls 2, Nicolas Robine 5, Herbert K Lyerly 7, Gregory J Hannon 8

Affiliations

  • 1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • 2Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • 3Department of Pathology & Laboratory Medicine, East Carolina University Brody School of Medicine, Greenville, NC, USA.
  • 4Department of Surgery, Duke University Medical Center, Durham, NC, USA.
  • 5New York Genome Center, New York, NY, USA.
  • 6Department of Dermatology, Boston University School of Medicine, Boston, MA, USA.
  • 7Department of Surgery, Duke University Medical Center, Durham, NC, USA.
  • 8Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
#Contributed equally.

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