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The CHEK2 gene and inherited breast cancer susceptibility

Oncogene volume 25, pages 5912–5919 (2006)Cite this article

Abstract

Checkpoint kinase 2 (CHEK2, Chk2) emerges as an important signal transducer of cellular responses to DNA damage and a candidate tumor suppressor whose defects contribute to molecular pathogenesis of diverse types of human malignancies, both sporadic and hereditary. Here, we briefly outline the molecular properties, regulation and physiological role of CHEK2, and review in more detail its defects that predispose to tumors, with particular emphasis on familial breast cancer. The frequency, penetrance and epidemiological as well as clinical significance of the two most studied breast cancer-predisposing variants of the CHEK2 gene, 1100delC and I157T, are highlighted in more depth, and additional CHEK2 mutations and their cancer relevance are discussed as well. These recent findings are considered also from a broader perspective of CHEK2 as the integral component of the ataxia telangiectasia-mutated-CHEK2-p53 pathway within the genome integrity maintenance system and a barrier against tumor progression. Finally, the potential value of information about the CHEK2 status in family counseling and optimizition of individualized cancer treatment is discussed.

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Acknowledgements

We thank our two research groups for unpublished data and inspiring discussions. The work in the authors' laboratories is supported by the Academy of Finland, Helsinki University Research Funds, the Finnish Cancer Society and Sigrid Juselius Foundation, the Danish Cancer Society, the Danish National Research Fund and the European Commission (Integrated projects ‘Mutant p53’, ‘Active p53’ and ‘DNA Repair’. We apologize to colleagues in the field whose work could only be quoted indirectly in this review article.

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  1. Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland

    H Nevanlinna

  2. Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Copenhagen, Denmark

    J Bartek

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  1. H Nevanlinna
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Correspondence to H Nevanlinna.

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Nevanlinna, H., Bartek, J. The CHEK2 gene and inherited breast cancer susceptibility. Oncogene 25, 5912–5919 (2006). https://doi.org/10.1038/sj.onc.1209877

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