title: Extending the phenotypes associated with DICER1 mutations.
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.
authors: Program in Cancer Genetics, Department of Oncology, McGill University, Montreal, Quebec, Canada. william.foulkes@mcgill.ca
authors: William D
authors: WD
authors: Foulkes
authors: Amin
authors: A
authors: Bahubeshi
authors: Nancy
authors: N
authors: Hamel
authors: Barbara
authors: B
authors: Pasini
authors: Sofia
authors: S
authors: Asioli
authors: Gareth
authors: G
authors: Baynam
authors: Catherine S
authors: CS
authors: Choong
authors: Adrian
authors: A
authors: Charles
authors: Richard P
authors: RP
authors: Frieder
authors: Megan K
authors: MK
authors: Dishop
authors: Nicole
authors: N
authors: Graf
authors: Mesiha
authors: M
authors: Ekim
authors: Dorothée
authors: D
authors: Bouron-Dal Soglio
authors: Jocelyne
authors: J
authors: Arseneau
authors: Robert H
authors: RH
authors: Young
authors: Nelly
authors: N
authors: Sabbaghian
authors: Archana
authors: A
authors: Srivastava
authors: Marc D
authors: MD
authors: Tischkowitz
authors: John R
authors: JR
authors: Priest
mesh_terms: D000293:Adolescent; D000328:Adult; D001998:Bronchopulmonary Sequestration / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D044483:Intestinal Polyposis / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D009386:Neoplastic Syndromes, Hereditary; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D018233:Rhabdomyosarcoma, Embryonal / Q000235:genetics* / Q000473:pathology; D043244:Ribonuclease III / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology
chemical_list: C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases