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Gene expression profiling assigns CHEK2 1100delC breast cancers to the luminal intrinsic subtypes

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Abstract

CHEK2 1100delC is a moderate-risk cancer susceptibility allele that confers a high breast cancer risk in a polygenic setting. Gene expression profiling of CHEK2 1100delC breast cancers may reveal clues to the nature of the polygenic CHEK2 model and its genes involved. Here, we report global gene expression profiles of a cohort of 155 familial breast cancers, including 26 CHEK2 1100delC mutant tumors. In line with previous work, all CHEK2 1100delC mutant tumors clustered among the hormone receptor-positive breast cancers. In the hormone receptor-positive subset, a 40-gene CHEK2 signature was subsequently defined that significantly associated with CHEK2 1100delC breast cancers. The identification of a CHEK2 gene signature implies an unexpected biological homogeneity among the CHEK2 1100delC breast cancers. In addition, all 26 CHEK2 1100delC tumors classified as luminal intrinsic subtype breast cancers, with 8 luminal A and 18 luminal B tumors. This biological make-up of CHEK2 1100delC breast cancers suggests that a relatively limited number of additional susceptibility alleles are involved in the polygenic CHEK2 model. Identification of these as-yet-unknown susceptibility alleles should be aided by clues from the 40-gene CHEK2 signature.

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Acknowledgments

We are grateful to the breast cancer patients and their clinicians for participation in this research. We thank Marion Meier-van Gelder, Mieke Timmermans, Miranda Arnold, Anneke Goedheer, Roberto Rodriguez-Garcia, Wendy van der Smissen, and Anja de Snoo for their technical assistance. We also thank Wim van Putten and Antoinette Hollestelle for insightful discussions. Funding : Dutch Cancer Society grants DDHK 2002-2687 and DDHK 2003-2862, and partly by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research NWO. Hanne Meijers-Heijboer is a fellow from the NWO Vidi Research Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Medical Oncology, Josephine Nefkens Institute, Erasmus University Medical Center, PO Box 1738, 3000 DR, Rotterdam, The Netherlands

    Jord H. A. Nagel, Marcel Smid, Anieta M. Sieuwerts, Marijke Wasielewski, Vanja de Weerd, Anita M. A. C. Trapman-Jansen, Jan G. M. Klijn, John A. Foekens, John W. M. Martens, Mieke Schutte & Hanne Meijers-Heijboer

  2. Department of Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands

    Justine K. Peeters & Peter J. van der Spek

  3. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands

    Ans van den Ouweland, Hennie Brüggenwirth & Hanne Meijers-Heijboer

  4. Erasmus Center for Biomics, Erasmus University Medical Center, Rotterdam, The Netherlands

    Wilfred F. J. van IJcken

  5. Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands

    Hanne Meijers-Heijboer

Authors
  1. Jord H. A. Nagel
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  2. Justine K. Peeters
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  4. Anieta M. Sieuwerts
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  7. Anita M. A. C. Trapman-Jansen
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  8. Ans van den Ouweland
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  10. Wilfred F. J. van IJcken
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  11. Jan G. M. Klijn
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  12. Peter J. van der Spek
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  13. John A. Foekens
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  14. John W. M. Martens
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  15. Mieke Schutte
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  16. Hanne Meijers-Heijboer
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Corresponding author

Correspondence to John W. M. Martens.

Additional information

Jord H. A. Nagel, Justine K. Peeters, and Marcel Smid contributed equally to this work.

John W. M. Martens, Mieke Schutte, and Hanne Meijers-Heijboer contributed equally to this work.

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Nagel, J.H.A., Peeters, J.K., Smid, M. et al. Gene expression profiling assigns CHEK2 1100delC breast cancers to the luminal intrinsic subtypes. Breast Cancer Res Treat 132, 439–448 (2012). https://doi.org/10.1007/s10549-011-1588-x

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  • DOI: https://doi.org/10.1007/s10549-011-1588-x

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