The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype

MWG Ruijs, A Broeks, FH Menko, MGEM Ausems, Anja Wagner, Rogier Oldenburg, EJ Meijers-Heijboer, LJ (Laura) van 't Veer, S Verhoef

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Background: CHEK2 has previously been excluded as a major cause of Li-Fraumeni syndrome (LFS). One particular CHEK2 germline mutation, c.1100delC, has been shown to be associated with elevated breast cancer risk. The prevalence of CHEK2*1100delC differs between populations and has been found to be relatively high in the Netherlands. The question remains nevertheless whether CHEK2 germline mutations contribute to the Li-Fraumeni phenotype. Methods: We have screened 65 Dutch TP53-negative LFS/LFL candidate patients for CHEK2 germline mutations to determine their contribution to the LFS/LFL phenotype. Results: We identified six index patients with a CHEK2 sequence variant, four with the c.1100delC variant and two sequence variants of unknown significance, p.Phe328Ser and c.1096-?_1629+? del. Conclusion: Our data show that CHEK2 is not a major LFS susceptibility gene in the Dutch population. However, CHEK2 might be a factor contributing to individual tumour development in TP53-negative cancer-prone families.
Original languageUndefined/Unknown
JournalHereditary Cancer in Clinical Practice
Publication statusPublished - 2009

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  • EMC MGC-02-96-01

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