The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds.


Journal Article

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.

Full Text

Cited Authors

  • Siddiqui, R; Onel, K; Facio, F; Nafa, K; Diaz, LR; Kauff, N; Huang, H; Robson, M; Ellis, N; Offit, K

Published Date

  • January 2005

Published In

Volume / Issue

  • 4 / 2

Start / End Page

  • 177 - 181

PubMed ID

  • 15951970

Pubmed Central ID

  • 15951970

Electronic International Standard Serial Number (EISSN)

  • 1573-7292

International Standard Serial Number (ISSN)

  • 1389-9600

Digital Object Identifier (DOI)

  • 10.1007/s10689-004-1946-5


  • eng