The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds Academic Article uri icon


MeSH Major

  • Genes, p53
  • Li-Fraumeni Syndrome
  • Protein-Serine-Threonine Kinases


  • Li-Fraumeni syndrome (LFS) is a dominantly inherited cancer predisposition syndrome characterized by a wide spectrum of neoplasms occurring at young age. Germline mutations in the TP53 tumor suppressor gene have been identified in approximately 71 of LFS patients and 22 of Li-Fraumeni-like (LFL) patients. Mutations within the cell cycle checkpoint gene CHEK2 have also been reported in some patients with LFS, LFL, and phenotypically suggestive of LFS (PS-LFS) not carrying a TP53 mutation. In this study, we show that 7 of the 23 patients with LFS/LFL tested positive for deleterious mutations in p53. Fifteen of the remaining sixteen were not found to carry the CHEK2* 1100delCmutation. These results indicate that CHEK2*1100delC is not a common cause of LFS, LFL, or PS-LFS in North American kindreds not carrying a TP53 mutation. Of note, two patients were found to carry p53* R72P, which is of unknown clinical significance. Lack of segregation of this allele in one of these kindreds provides strong evidence that the R72P allele is not disease-causing. While mutations in p53 account for a proportion of patients with LFS/LFL, future studies are needed to determine if other genes are responsible for LFS/LFL families not carrying germline p53 mutations.

publication date

  • June 2005



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1007/s10689-004-1946-5

PubMed ID

  • 15951970

Additional Document Info

start page

  • 177

end page

  • 81


  • 4


  • 2