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Breast Cancer Research and Treatment

, Volume 132, Issue 2, pp 439–448 | Cite as

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

  • Jord H. A. Nagel
  • Justine K. Peeters
  • Marcel Smid
  • Anieta M. Sieuwerts
  • Marijke Wasielewski
  • Vanja de Weerd
  • Anita M. A. C. Trapman-Jansen
  • Ans van den Ouweland
  • Hennie Brüggenwirth
  • Wilfred F. J. van IJcken
  • Jan G. M. Klijn
  • Peter J. van der Spek
  • John A. Foekens
  • John W. M. Martens
  • Mieke Schutte
  • Hanne Meijers-Heijboer
Preclinical Study

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.

Keywords

Breast cancer CHEK2 1100delC Intrinsic subtypes 

Notes

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.

Conflict of interests

None.

Supplementary material

10549_2011_1588_MOESM1_ESM.pdf (69 kb)
Supplementary material 1 (PDF 69 kb)
10549_2011_1588_MOESM2_ESM.pdf (60 kb)
Supplementary material 2 (PDF 60 kb)
10549_2011_1588_MOESM3_ESM.pdf (14 kb)
Supplementary material 3 (PDF 14 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Jord H. A. Nagel
    • 1
  • Justine K. Peeters
    • 2
  • Marcel Smid
    • 1
  • Anieta M. Sieuwerts
    • 1
  • Marijke Wasielewski
    • 1
  • Vanja de Weerd
    • 1
  • Anita M. A. C. Trapman-Jansen
    • 1
  • Ans van den Ouweland
    • 3
  • Hennie Brüggenwirth
    • 3
  • Wilfred F. J. van IJcken
    • 4
  • Jan G. M. Klijn
    • 1
  • Peter J. van der Spek
    • 2
  • John A. Foekens
    • 1
  • John W. M. Martens
    • 1
  • Mieke Schutte
    • 1
  • Hanne Meijers-Heijboer
    • 1
    • 3
    • 5
  1. 1.Department of Medical OncologyJosephine Nefkens Institute, Erasmus University Medical CenterRotterdamThe Netherlands
  2. 2.Department of BioinformaticsErasmus University Medical CenterRotterdamThe Netherlands
  3. 3.Department of Clinical GeneticsErasmus University Medical CenterRotterdamThe Netherlands
  4. 4.Erasmus Center for BiomicsErasmus University Medical CenterRotterdamThe Netherlands
  5. 5.Department of Clinical GeneticsVU Medical CenterAmsterdamThe Netherlands

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