title: The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, The Netherlands. mwg.ruijs@vumc.nl
authors.forename: Marielle W G
authors.initials: MW
authors.lastname: Ruijs
authors.forename: Annegien
authors.initials: A
authors.lastname: Broeks
authors.forename: Fred H
authors.initials: FH
authors.lastname: Menko
authors.forename: Margreet G E M
authors.initials: MG
authors.lastname: Ausems
authors.forename: Anja
authors.initials: A
authors.lastname: Wagner
authors.forename: Rogier
authors.initials: R
authors.lastname: Oldenburg
authors.forename: Hanne
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van't Veer
authors.forename: Senno
authors.initials: S
authors.lastname: Verhoef