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

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32 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)439-448
JournalBreast cancer research and treatment
Volume132
Issue number2
DOIs
Publication statusPublished - 2012

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