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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.

Publication ,  Journal Article
Rebbeck, CA; Xian, J; Bornelöv, S; Geradts, J; Hobeika, A; Geiger, H; Alvarez, JF; Rozhkova, E; Nicholls, A; Robine, N; Lyerly, HK; Hannon, GJ
Published in: Nat Commun
June 13, 2022

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 13, 2022

Volume

13

Issue

1

Start / End Page

3399

Location

England

Related Subject Headings

  • Transcriptome
  • Transcription Factors
  • Humans
  • Homeodomain Proteins
  • Female
  • Disease Progression
  • Carcinoma, Intraductal, Noninfiltrating
  • Carcinoma, Ductal, Breast
  • Breast Neoplasms
  • Biomarkers, Tumor
 

Citation

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Rebbeck, C. A., Xian, J., Bornelöv, S., Geradts, J., Hobeika, A., Geiger, H., … Hannon, G. J. (2022). Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma. Nat Commun, 13(1), 3399. https://doi.org/10.1038/s41467-022-30573-4
Rebbeck, Clare A., Jian Xian, Susanne Bornelöv, Joseph Geradts, Amy Hobeika, Heather Geiger, Jose Franco Alvarez, et al. “Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.Nat Commun 13, no. 1 (June 13, 2022): 3399. https://doi.org/10.1038/s41467-022-30573-4.
Rebbeck, Clare A., et al. “Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.Nat Commun, vol. 13, no. 1, June 2022, p. 3399. Pubmed, doi:10.1038/s41467-022-30573-4.
Rebbeck CA, Xian J, Bornelöv S, Geradts J, Hobeika A, Geiger H, Alvarez JF, Rozhkova E, Nicholls A, Robine N, Lyerly HK, Hannon GJ. Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma. Nat Commun. 2022 Jun 13;13(1):3399.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 13, 2022

Volume

13

Issue

1

Start / End Page

3399

Location

England

Related Subject Headings

  • Transcriptome
  • Transcription Factors
  • Humans
  • Homeodomain Proteins
  • Female
  • Disease Progression
  • Carcinoma, Intraductal, Noninfiltrating
  • Carcinoma, Ductal, Breast
  • Breast Neoplasms
  • Biomarkers, Tumor