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

doi:10.1186/1897-4287-7-4

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

Clinical Genetics

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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. 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 language	Undefined/Unknown
Journal	Hereditary Cancer in Clinical Practice
Volume	7
DOIs	https://doi.org/10.1186/1897-4287-7-4
Publication status	Published - 2009

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Cite this

@article{94adfa34e32345dda191a2eae54fa6f6,

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. 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.",

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

year = "2009",

doi = "10.1186/1897-4287-7-4",

language = "Undefined/Unknown",

volume = "7",

journal = "Hereditary Cancer in Clinical Practice",

issn = "1731-2302",

publisher = "BioMed Central Ltd.",

}

TY - JOUR

T1 - The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype

AU - Ruijs, MWG

AU - Broeks, A

AU - Menko, FH

AU - Ausems, MGEM

AU - Wagner, Anja

AU - Oldenburg, Rogier

AU - Meijers-Heijboer, EJ

AU - van 't Veer, LJ (Laura)

AU - Verhoef, S

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1186/1897-4287-7-4

DO - 10.1186/1897-4287-7-4

M3 - Article

SN - 1731-2302

VL - 7

JO - Hereditary Cancer in Clinical Practice

JF - Hereditary Cancer in Clinical Practice

ER -