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


Authors: Siddiqui, R.; Onel, K.; Facio, F.; Nafa, K.; Diaz, L. R.; Kauff, N.; Huang, H.; Robson, M.; Ellis, N.; Offit, K.
Article Title: The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds
Abstract: 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. © Springer 2005.
Keywords: adolescent; adult; child; clinical article; controlled study; child, preschool; middle aged; gene mutation; gene deletion; polymorphism, single nucleotide; phenotype; allele; genetic association; gene frequency; mutational analysis; protein p53; pedigree; protein-serine-threonine kinases; checkpoint kinase 2; familial cancer; li-fraumeni syndrome; dna mutational analysis; germ-line mutation; genes, p53; polymorphism; tp53; germline mutations; chek2; 1100delc
Journal Title: Familial Cancer
Volume: 4
Issue: 2
ISSN: 1389-9600
Publisher: Springer  
Date Published: 2005-01-01
Start Page: 177
End Page: 181
Language: English
DOI: 10.1007/s10689-004-1946-5
PUBMED: 15951970
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 10" - "Export Date: 24 October 2012" - "CODEN: FCAAA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Kenneth Offit
    519 Offit
  2. Khedoudja Nafa
    184 Nafa
  3. Mark E Robson
    368 Robson
  4. Noah Kauff
    122 Kauff
  5. Nathan A Ellis
    74 Ellis
  6. Helen Huang
    13 Huang
  7. Flavia M Facio
    3 Facio