Gene expression profiling assigns CHEK2 1100delC breast cancers to the luminal intrinsic subtypes |
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Authors: | Nagel Jord H A Peeters Justine K Smid Marcel Sieuwerts Anieta M Wasielewski Marijke de Weerd Vanja Trapman-Jansen Anita M A C van den Ouweland Ans Brüggenwirth Hennie van I Jcken Wilfred F J Klijn Jan G M van der Spek Peter J Foekens John A Martens John W M Schutte Mieke Meijers-Heijboer Hanne |
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Affiliation: | Department of Medical Oncology, Josephine Nefkens Institute, Erasmus University Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands. |
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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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