Abstract
KLLN is a p53 target gene with DNA binding function and represents a highly plausible candidate breast cancer predisposition gene. We screened for predisposing variants in 860 high-risk breast cancer families using high resolution melt analysis. A germline c.339_340delAG variant predicted to cause premature termination of the protein after 57 alternative amino acid residues was identified in 3/860 families who tested negative for BRCA1 and BRCA2 mutations and in 1/84 sporadic breast cancer cases. However, the variant was also detected in 2/182 families with known BRCA1 or BRCA2 mutations and in 2/464 non-cancer controls. Furthermore, loss of the mutant allele was detected in 2/2 breast tumors. Our data suggest that pathogenic mutations in KLLN are rare in breast cancer families and the c.339_340delAG variant does not represent a high-penetrance breast cancer risk allele.
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This work was supported by the Victorian Breast Cancer Research Consortium.
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IGC and GM conceived of the study; ERT and DYHC carried out experiments and analyzed data; KLG interpreted data and generated the figure; IGC, KLG, and ERT were involved in writing the paper. All authors had final approval of the submitted and published versions.
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Thompson, E.R., Gorringe, K.L., Choong, D.Y.H. et al. Analysis of KLLN as a high-penetrance breast cancer predisposition gene. Breast Cancer Res Treat 134, 543–547 (2012). https://doi.org/10.1007/s10549-012-2088-3
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DOI: https://doi.org/10.1007/s10549-012-2088-3