• Leanne de Kock, Nelly Sabbaghian, Soglio Dorothée Bouron-Dal DB, R Paul Guillerman, Byung-Kiu Park, Rose Chami, Cheri L Deal, John R Priest, and William D Foulkes.
• Department of Human Genetics (L.d.K.) and Program in Cancer Genetics, Department of Oncology and Human Genetics (W.D.F.), McGill University, Montreal, Quebec H2W 1S6, Canada; Lady Davis Institute (L.d.K., N.S.), Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada; Department of Pathology (D.B.-D.S., R.C.) and Endocrine Service (C.L.D.), CHU-Sainte Justine and University of Montreal, Montreal, Quebec H3T 1C5, Canada; Department of Pediatric Radiology (R.P.G.), Baylor College of Medicine, Texas Children's Hospital, Houston, Texas 77030; Center for Pediatric Oncology (B.-K.P.), National Cancer Center, Goyang-si, South Korea 410-769; and (J.R.P.) Minneapolis, Minnesota 55454.
• J. Clin. Endocrinol. Metab. 2014 Jun 1; 99 (6): E1072-7.

ContextCarriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome. Thyroid abnormalities are a common finding in DICER1 syndrome with multinodular goiter frequently present in many families in which a germline DICER1 mutation is segregating. Differentiated thyroid carcinoma (DTC) is infrequently seen in such pedigrees. In addition to germline DICER1 mutations, specific somatic mutations have been identified in the DICER1 ribonuclease IIIb catalytic domain in several tumor types.ObjectiveWe aimed to determine whether such characteristic somatic DICER1 mutations are present in DTCs that arise within germline DICER1 mutation carriers.Design And SettingThe study involved an opportunistic collection of 3 cases of DTC arising in individuals suspected to have DICER1 syndrome and hospital-based ascertainment and testing was implemented.ResultsWe identified somatic DICER1 mutations in 3 DTCs arising in unrelated germline DICER1 mutation carriers, all of whom had been diagnosed in infancy with pleuropulmonary blastoma (PPB), were treated with chemotherapy, exposed frequently to diagnostic radiation, and subsequently developed DTC. The somatic mutations occurred within the DICER1 ribonuclease IIIb domain, affecting highly conserved amino acid residues central to the catalytic activity of the domain.ConclusionThis report of somatic DICER1 mutations in DTC strengthens the association between DTC and the DICER1 syndrome. The possible association between germline DICER1 mutations, PPB treatment, and the risk of subsequent DTC must be considered by clinicians when treating PPB.

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