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