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Extending the phenotypes associated with DICER1 mutations

Authors

  • William D. Foulkes,

    Corresponding author
    1. Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada
    2. Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada
    3. The Research Institute, McGill University Health Centre, Montreal, Quebec, Canada
    • Program in Cancer Genetics, Departments of Oncology and Human Genetics, Gerald Bronfman Centre for Clinical Research in Oncology, McGill University, 546 Pine Ave West, Montréal, QC H2W 1S6, Canada.
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  • Amin Bahubeshi,

    1. Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada
    2. Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada
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  • Nancy Hamel,

    1. Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada
    2. The Research Institute, McGill University Health Centre, Montreal, Quebec, Canada
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  • Barbara Pasini,

    1. Departments of Genetics, Biology and Biochemistry
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  • Sofia Asioli,

    1. Biomedical Sciences and Human Oncology, University of Turin, Italy
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  • Gareth Baynam,

    1. Genetic Services of Western Australia, Western Australia, Australia
    2. School of Paediatrics and Child Health, University of Western Australia, Australia
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  • Catherine S. Choong,

    1. School of Paediatrics and Child Health, University of Western Australia, Australia
    2. Department of Endocrinology, Princess Margaret Hospital for Children, Western Australia, Australia
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  • Adrian Charles,

    1. School of Pathology, University of Western Australia, Australia
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  • Richard P. Frieder,

    1. Cancer Risk Assessment & Prevention, Santa Monica and Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, California
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  • Megan K. Dishop,

    1. Department of Pathology, Children's Hospital Colorado and University of Colorado-Denver School of Medicine, Aurora, Colorado
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  • Nicole Graf,

    1. Department of Pathology, The Children's Hospital at Westmead, Westmead, Sydney, New South Wales, Australia
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  • Mesiha Ekim,

    1. Department of Pediatric Nephrology, School of Medicine, Ankara University, Ankara, Turkey
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  • Dorothée Bouron-Dal Soglio,

    1. Department of Pathology, CHU Sainte Justine, Montréal, Quebec, Canada
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  • Jocelyne Arseneau,

    1. Department of Pathology, McGill University, Montreal, Quebec, Canada
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  • Robert H. Young,

    1. Department of Pathology, Massachusetts General Hospital, Harvard University, Boston, Massachusetts
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  • Nelly Sabbaghian,

    1. Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada
    2. Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada
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  • Archana Srivastava,

    1. Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada
    2. Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada
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  • Marc D. Tischkowitz,

    1. Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada
    2. Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada
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  • John R. Priest

    1. The International Pleuropulmonary Blastoma Registry, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota
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  • Communicated by Ravi Savarirayan

Abstract

DICER1 is crucial for embryogenesis and early development. Forty different heterozygous germline DICER1 mutations have been reported worldwide in 42 probands that developed as children or young adults, pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian sex cord-stromal tumors (especially Sertoli-Leydig cell tumor [SLCT]), and/or multinodular goiter (MNG). We report DICER1 mutations in seven additional families that manifested uterine cervix embryonal rhabdomyosarcoma (cERMS, four cases) and primitive neuroectodermal tumor (cPNET, one case), Wilms tumor (WT, three cases), pulmonary sequestration (PS, one case), and juvenile intestinal polyp (one case). One carrier developed (age 25 years) a pleomorphic sarcoma of the thigh; another carrier had transposition of great arteries (TGA). These observations show that cERMS, cPNET, WT, PS, and juvenile polyps fall within the spectrum of DICER1-related diseases. DICER1 appears to be the first gene implicated in the etiology of cERMS, cPNET, and PS. Young adulthood sarcomas and perhaps congenital malformations such as TGA may also be associated. 32:1381–1384, 2011. ©2011 Wiley Periodicals, Inc.

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