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High frequency of de novo mutations in Li–Fraumeni syndrome
  1. K D Gonzalez1,2,
  2. C H Buzin1,2,
  3. K A Noltner2,
  4. D Gu2,3,
  5. W Li2,
  6. D Malkin4,
  7. S S Sommer1,2
  1. 1
    MEDomics, Azusa, California, USA
  2. 2
    Department of Molecular Genetics, City of Hope, Duarte, California, USA
  3. 3
    Bioinformatics Group, Department of Molecular Diagnosis, City of Hope, Duarte, California, USA
  4. 4
    Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr S S Sommer, MEDomics, LLC, 426 N. San Gabriel Ave, Azusa, CA 91702, USA; ssommer{at}


Background: Li–Fraumeni syndrome is an autosomal dominant cancer predisposition syndrome caused by germline mutations in the TP53 gene. The frequency of germline de novo TP53 mutations is largely unknown; few unequivocal de novo mutations have been reported.

Methods and results: Of 341 patients with early onset cancer sent for clinical testing to a national reference laboratory, 75 patients had TP53 germline mutations. Five (7%) de novo mutations were identified, as well as an additional 10 TP53 germline mutations likely to be de novo by family history. The frequency of de novo TP53 mutations in this patient sample is at least 7% and may be as high as 20%.

Conclusions: The possibility that de novo germline TP53 mutations are relatively common has implications for testing and the identification of potential Li–Fraumeni syndrome in patients with little or no family history of cancer.

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  • Funding Supported in part from a grant from the National Cancer Institute of Canada (to DM) with funds from the Canadian Cancer Society.

  • Competing interests None.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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