Somatic TP53 mutation mosaicism in a patient with Li–Fraumeni syndrome

Authors

  • Kamila Prochazkova,

    1. Department of Biology and Medical Genetics, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic
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  • Kristyna Pavlikova,

    1. Department of Biology and Medical Genetics, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic
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  • Marek Minarik,

    1. Laboratory for Molecular Genetics and Oncology, Genomac International, Prague, Czech Republic
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  • David Sumerauer,

    1. Department of Pediatric Hematology and Oncology, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic
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  • Roman Kodet,

    1. Department of Pathology and Molecular Medicine, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic
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  • Zdenek Sedlacek

    Corresponding author
    1. Department of Biology and Medical Genetics, Charles University 2nd Medical School and University Hospital Motol, Prague, Czech Republic
    • Department of Biology and Medical Genetics, Charles University 2nd Medical School and University Hospital Motol, V Uvalu 84, 15006 Prague 5, Czech Republic.
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  • How to cite this article: Prochazkova K, Pavlikova K, Minarik M, Sumerauer D, Kodet R, Sedlacek Z. 2009. Somatic TP53 mutation mosaicism in a patient with Li–Fraumeni syndrome. Am J Med Genet Part A 149A:206–211.

Abstract

We present a girl who developed adrenocortical adenoma at the age of 1 year and osteosarcoma at the age of 5 years. There was no history of cancer in her parents and their relatives. However, both tumors were typical for the Li–Fraumeni syndrome (LFS), and the patient met criteria for germline TP53 mutation testing. A mutation in codon 282 (Arg282Trp) was identified in her blood lymphocyte genomic DNA. The substitution was found in neither of her parents, which indicated a possibility of a de novo mutation. Unexpectedly, sequencing of the DNA of the patient repeatedly showed allelic imbalance in favor of the normal allele. This observation prompted us to investigate the putative somatic mosaicism in the patient consisting of normal cells and cells heterozygous for the mutation. The imbalance was also examined in two other non-invasively sampled tissues, buccal cells, and cells from the urine sediment, and sequencing was confirmed with two other independent methods. While the findings in blood and the urine sediment were similar, in buccal cells both alleles were present in equal amounts. The allele ratio in lymphocytes was consistent with a mosaic where about 2/3 of cells carried two normal alleles and only 1/3 was heterozygous for the mutation. Despite the mosaicism the girl developed two early childhood tumors of mesodermal origin, and her phenotype was thus not milder than that of other germline TP53 mutation carriers. To our knowledge this is the first description of somatic mosaicism for a de novo TP53 mutation in LFS. © 2008 Wiley-Liss, Inc.

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