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

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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.

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Abbreviations

LFL:

Li-Fraumeni-like

LFS:

Li-Fraumeni-syndrome

PS-LFS:

phenotypically suggestive of Li-Fraumeni-syndrome

SNP:

single nucleotide polymorphism

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Authors and Affiliations

  1. Memorial Sloan Kettering Cancer Center, Clinical Genetics Service, Department of Medicine, New York, 10021, NY, 1275 York Avenue, USA

    Rina Siddiqui, Flavia Facio, Kedoudja Nafa, Noah Kauff, Helen Huang, Mark Robson, Nathan Ellis & Kenneth Offit

  2. Hospital Universitario Doce de Octubre, Madrid, Spain

    Louis Robles Diaz

  3. Department of Pediatrics, University of Chicago, Chicago, Illinois, USA

    Kenan Onel

Authors
  1. Rina Siddiqui
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  2. Kenan Onel
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  3. Flavia Facio
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  4. Kedoudja Nafa
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  5. Louis Robles Diaz
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  6. Noah Kauff
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  7. Helen Huang
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  8. Mark Robson
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  9. Nathan Ellis
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  10. Kenneth Offit
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Corresponding author

Correspondence to Kenneth Offit.

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

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  • DOI: https://doi.org/10.1007/s10689-004-1946-5

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