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CHEK2 variants: linking functional impact to cancer risk

Boonen, Rick A.C.M., Vreeswijk, Maaike P.G., van Attikum, Haico·2022·Trends in Cancer
DOI 10.1016/j.trecan.2022.04.009
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Abstract

Protein-truncating variants in the breast cancer susceptibility gene CHEK2 are associated with a moderately increased risk of breast cancer. By contrast, for missense variants of uncertain significance (VUS) in CHEK2 the associated breast cancer risk is often unclear. To facilitate their classification, functional assays that determine the impact of missense VUS on CHK2 protein function have been performed. Here we discuss these functional analyses that consistently reveal an association between impaired protein function and increased breast cancer risk. Overall, these findings suggest that damaging CHEK2 missense VUS are associated with a risk of breast cancer similar to that of protein-truncating variants. This indicates the urgency of expanding the functional characterization of CHEK2 missense VUS to further understand the associated cancer risk.

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Metadata

Authors
Boonen, R. A. C. M., Vreeswijk, M. P. G., & van Attikum, H.
Venue
Trends in Cancer
Publisher
Elsevier BV
Published
2022-09
Volume
8
Issue
9
Pages
759-770
ISSN
2405-8033
DOI
10.1016/j.trecan.2022.04.009
Cited by
49
References
4
Language
en
Licence
Funders
KWF Kankerbestrijding (KWF/Pink Ribbon 11704, KWF-CRAFT 12754)

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