title: Ovarian embryonal rhabdomyosarcoma is a rare manifestation of the DICER1 syndrome.
abstract: Embryonal rhabdomyosarcoma (ERMS), a soft tissue sarcoma, is one of the most common pediatric cancers. Certain ERMSs are associated with the DICER1 syndrome, a tumor predisposition syndrome caused by germ-line DICER1 mutations. Characteristic somatic mutations have also been identified in DICER1-associated tumor types. These "hotspot" mutations affect the catalytic activity of the DICER1 ribonuclease IIIb domain. Primary ovarian ERMS (oERMS) is extremely rare. We present a case of a 6-year-old girl with an oERMS harboring 2 DICER1 mutations. The girl also exhibited other DICER1 phenotypes: cystic nephroma (CN) and multinodular goiter. Somatic investigations of the CN identified a hotspot DICER1 mutation different from that in the oERMS. Significantly, the CN presented at 12 years of age, which is much older than the previously reported age range of susceptibility. This report documents the occurrence of DICER1 mutations in a case of oERMS, expanding the spectrum of DICER1-associated tumors.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3A 0G4; Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2.
authors.forename: Leanne
authors.initials: L
authors.lastname: de Kock
authors.affiliation: Division of Hematology/Oncology, The Hospital for Sick Children, Department of Molecular and Medical Genetics, The University of Toronto, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Harriet
authors.initials: H
authors.lastname: Druker
authors.affiliation: Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3H 2R9.
authors.forename: Evan
authors.initials: E
authors.lastname: Weber
authors.affiliation: Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3H 2R9.
authors.forename: Nancy
authors.initials: N
authors.lastname: Hamel
authors.affiliation: Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Traubici
authors.affiliation: Division of Hematology/Oncology, The Hospital for Sick Children, Departments of Pediatrics Medical Biophysics, The University of Toronto, Toronto, Ontario, Canada M5G 1X8.
authors.forename: David
authors.initials: D
authors.lastname: Malkin
authors.affiliation: Department of Pathology, McGill University, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Arseneau
authors.affiliation: School for Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia WA 6008.
authors.forename: Colin J R
authors.initials: CJ
authors.lastname: Stewart
authors.affiliation: Department of Pathology, CHU-Sainte Justine and University of Montreal, Montréal, Quebec, Canada H3T 1C5.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Bouron-Dal Soglio
authors.affiliation: Minneapolis, MN 55414.
authors.forename: John R
authors.initials: JR
authors.lastname: Priest
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3A 0G4; Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2; Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3H 2R9; Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada H2W 1S6. Electronic address: william.foulkes@mcgill.ca.
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
mesh_terms: D002648:Child; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D018233:Rhabdomyosarcoma, Embryonal / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: DICER1; Embryonal rhabdomyosarcoma; Ovary; Pediatric tumors; miRNA