DICER1 mutations in embryonal rhabdomyosarcomas from children with and without familial PPB-tumor predisposition syndrome.

Embryonal rhabdomyosarcoma (ERMS) is the most common sarcoma of childhood and is a component of the familial Pleuropulmonary Blastoma (PPB)-predisposition syndrome. Using the PPB model, we hypothesized that DICER1 mutations would be found in familial and sporadic forms of ERMS. Blood samples from four children with familial PPB and ERMS, and an additional 52 sporadic ERMS tumors were tested for DICER1 mutations. DICER1 mutations were found in all 4 patients with familial PPB and in 2 of 52 (3.8%) patients with sporadic ERMS. Our findings confirm the pathogenetic relationship between ERMS and PPB and suggest that ERMS may result from abnormal miRNA regulation.