Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers

Authors

  • Simone Hettmer MD,

    Corresponding author
    1. Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Pediatric Hematology/ Oncology, Boston Children's Hospital, Boston, Massachusetts
    2. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
    3. Howard Hughes Medical Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, Massachusetts
    4. Joslin Diabetes Center, Boston, Massachusetts
    • Corresponding author: Simone Hettmer, MD, Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115; Fax: (617) 732-2593; simone.hettmer@childrens.harvard.edu

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  • Natasha M. Archer MD,

    1. Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Pediatric Hematology/ Oncology, Boston Children's Hospital, Boston, Massachusetts
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  • Gino R. Somers MBBS,

    1. Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
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  • Ana Novokmet BA,

    1. Division of Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
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  • Amy J. Wagers PhD,

    1. Howard Hughes Medical Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Cambridge, Massachusetts
    2. Joslin Diabetes Center, Boston, Massachusetts
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  • Lisa Diller MD,

    1. Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Pediatric Hematology/ Oncology, Boston Children's Hospital, Boston, Massachusetts
    2. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
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  • Carlos Rodriguez-Galindo MD,

    1. Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Pediatric Hematology/ Oncology, Boston Children's Hospital, Boston, Massachusetts
    2. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
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  • Lisa A. Teot MD,

    1. Department of Pathology, Boston Children's Hospital, Boston, Massachusetts
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  • David Malkin MD

    1. Division of Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
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Errata

This article is corrected by:

  1. Errata: Erratum: Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers Volume 120, Issue 12, 1910, Article first published online: 6 March 2014

  • The authors are grateful to Holcombe E. Grier for constructive comments on the manuscript.

Abstract

BACKGROUND

Rhabdomyosarcoma (RMS) represents a diverse category of myogenic malignancies with marked differences in molecular alterations and histology. This study examines the question if RMS predisposition due to germline TP53 mutations correlates with certain RMS histologies.

METHODS

The histology of RMS tumors diagnosed in 8 consecutive children with TP53 germline mutations was reviewed retrospectively. In addition, germline TP53 mutation analysis was performed in 7 children with anaplastic RMS (anRMS) and previously unknown TP53 status.

RESULTS

RMS tumors diagnosed in 11 TP53 germline mutation carriers all exhibited nonalveolar, anaplastic histology as evidenced by the presence of enlarged hyperchromatic nuclei with or without atypical mitotic figures. Anaplastic RMS was the first malignant diagnosis for all TP53 germline mutation carriers in this cohort, and median age at diagnosis was 40 months (mean, 40 months ± 15 months; range, 19-67 months). The overall frequency of TP53 germline mutations was 73% (11 of 15 children) in pediatric patients with anRMS. The frequency of TP53 germline mutations in children with anRMS was 100% (5 of 5 children) for those with a family cancer history consistent with Li-Fraumeni syndrome (LFS), and 80% (4 of 5 children) for those without an LFS cancer phenotype.

CONCLUSIONS

Individuals harboring germline TP53 mutations are predisposed to develop anRMS at a young age. If future studies in larger anRMS cohorts confirm the findings of this study, the current Chompret criteria for LFS should be extended to include children with anRMS irrespective of family history. Cancer 2014;120:1068–1075. © 2013 American Cancer Society.

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