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

Rina Siddiqui, Kenan Onel, Flavia Facio, Kedoudja Nafa, Louis Robles Diaz, Noah Kauff, Helen Huang, Mark Robson, Nathan Ellis, Kenneth Offit

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)177-181
Number of pages5
JournalFamilial Cancer
Volume4
Issue number2
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Li-Fraumeni Syndrome
Mutation
Germ-Line Mutation
Alleles
cdc Genes
Tumor Suppressor Genes
Neoplasms

Keywords

  • 1100delC
  • CHEK2
  • Germline mutations
  • Li-Fraumeni syndrome
  • Polymorphism
  • TP53

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Siddiqui, R., Onel, K., Facio, F., Nafa, K., Diaz, L. R., Kauff, N., ... Offit, K. (2005). The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds. Familial Cancer, 4(2), 177-181. https://doi.org/10.1007/s10689-004-1946-5

The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds. / Siddiqui, Rina; Onel, Kenan; Facio, Flavia; Nafa, Kedoudja; Diaz, Louis Robles; Kauff, Noah; Huang, Helen; Robson, Mark; Ellis, Nathan; Offit, Kenneth.

In: Familial Cancer, Vol. 4, No. 2, 06.2005, p. 177-181.

Research output: Contribution to journalArticle

Siddiqui, R, Onel, K, Facio, F, Nafa, K, Diaz, LR, Kauff, N, Huang, H, Robson, M, Ellis, N & Offit, K 2005, 'The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds', Familial Cancer, vol. 4, no. 2, pp. 177-181. https://doi.org/10.1007/s10689-004-1946-5
Siddiqui, Rina ; Onel, Kenan ; Facio, Flavia ; Nafa, Kedoudja ; Diaz, Louis Robles ; Kauff, Noah ; Huang, Helen ; Robson, Mark ; Ellis, Nathan ; Offit, Kenneth. / The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds. In: Familial Cancer. 2005 ; Vol. 4, No. 2. pp. 177-181.
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AB - 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.

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