Premium
Extending the phenotypes associated with DICER1 mutations
Author(s) -
Foulkes William D.,
Bahubeshi Amin,
Hamel Nancy,
Pasini Barbara,
Asioli Sofia,
Baynam Gareth,
Choong Catherine S.,
Charles Adrian,
Frieder Richard P.,
Dishop Megan K.,
Graf Nicole,
Ekim Mesiha,
BouronDal Soglio Dorothée,
Arseneau Jocelyne,
Young Robert H.,
Sabbaghian Nelly,
Srivastava Archana,
Tischkowitz Marc D.,
Priest John R.
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21600
Subject(s) - biology , embryonal rhabdomyosarcoma , germline , proband , rhabdomyosarcoma , sarcoma , germline mutation , phenotype , cancer research , pathology , mutation , gene , genetics , medicine
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.