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Tumor Protein p53 (TP53) Testing and Li-Fraumeni Syndrome

Current Status of Clinical Applications and Future Directions

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Abstract

Prevalent as an acquired abnormality in cancer, the role of tumor protein p53 (TP53) as a germline mutation continues to evolve. The clinical impact of a germline TP53 mutation is often dramatic and affects the full life course, with a propensity to develop rare tumors in childhood and multiple common cancers of unexpectedly early onset in adulthood. In this article, we review the clinical relevance of germline mutations in the TP53 tumor suppressor gene to current healthcare practice, including the optimal ways to identify patients with Li-Fraumeni syndrome (LFS), to recognize the core cancers associated with LFS, and to develop strategies for early detection of LFS-associated tumors. Several TP53-targeted approaches to improve outcomes in LFS patients are also reviewed. A case report is used to highlight special TP53 testing dilemmas and unique challenges associated with genetic testing decisions in the current age of rapidly advancing genomic technologies.

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Acknowledgements

The project described in this article was supported in part by grant numbers RC4CA153828 and R25CA085771 (principal investigator: J. Weitzel) from the National Cancer Institute. The content of the article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The authors wish to acknowledge Tracy Sulkin for assistance with manuscript preparation.

Conflicts of Interest

The authors state that they have no financial relationship with the funders of this work, and no other conflicts of interest that are directly relevant to the content of this article.

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  1. Division of Clinical Cancer Genetics, Department of Pediatrics, City of Hope, Duarte, CA, USA

    April D. Sorrell

  2. Division of Clinical Cancer Genetics, Department of Population Sciences, City of Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA

    April D. Sorrell, Carin R. Espenschied, Julie O. Culver & Jeffrey N. Weitzel

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  1. April D. Sorrell
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  2. Carin R. Espenschied
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Sorrell, A.D., Espenschied, C.R., Culver, J.O. et al. Tumor Protein p53 (TP53) Testing and Li-Fraumeni Syndrome. Mol Diagn Ther 17, 31–47 (2013). https://doi.org/10.1007/s40291-013-0020-0

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