Extending the Phenotypes Associated with DICER1 Mutations.

DICER1 is crucial for embryogenesis and early development. Forty different heterozygous germ-line DICER1 mutations have been reported world-wide in 42 probands who developed, as children or young adults, pleuropulmonary blastoma, cystic nephroma, ovarian sex cord stromal tumors (especially Sertoli-Leydig cell tumor) and/or multi-nodular goiter. We report DICER1 mutations in seven additional families who 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 like TGA may also be associated.