Embryonal rhabdomyosarcoma in a patient with a heterozygous frameshift variant in the DICER1 gene and additional manifestations of the DICER1 syndrome

Fam Cancer. 2017 Jul;16(3):401-405. doi: 10.1007/s10689-016-9958-5.


Germline mutations in the DICER1 gene are associated with an inherited cancer predisposition syndrome also known as the DICER1-syndrome, which is implicated in a broad range of tumors including pleuropulmonary blastoma, ovarian Sertoli-Leydig cell tumors, ciliary body medulloepithelioma (CBME), pituitary blastoma, embryonal rhabdomyosarcoma (eRMS), anaplastic renal sarcoma as well as ocular, sinonasal tumors ovarian sex-cord tumors, thyroid neoplasia and cystic nephroma. This study describes a novel, heterozygous frameshift DICER1 mutation in a patient, who is affected by different tumors of the DICER1-syndrome, including eRMS, CBME and suspected pleuropulmonary blastoma type I. By whole-exome sequencing of germline material using peripheral blood-derived DNA, we identified a single base pair duplication within the DICER1 gene (c.3405 dupA) that leads to a frameshift and results in a premature stop in exon 21 (p.Gly1136Arg). The metachronous occurrence of two unrelated tumor entities (eRMS and CBME) in a very young child within a short timeframe should have raised the suspicion of an underlying cancer susceptibility syndrome and should be prompt tested for DICER1.

Keywords: DICER1 germline mutation; DICER1-syndrome; Embryonal rhabdomyosarcoma; Focal nodular hyperplasia; Frameshift; Medulloepithelioma; Pleuropulmonary blastoma; Renal cysts.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics
  • Child
  • DEAD-box RNA Helicases / genetics*
  • Female
  • Frameshift Mutation
  • Genetic Predisposition to Disease / genetics
  • Heterozygote
  • Humans
  • Neoplastic Syndromes, Hereditary / genetics*
  • Neuroectodermal Tumors, Primitive / genetics
  • Pulmonary Blastoma / genetics
  • Rhabdomyosarcoma, Embryonal / genetics*
  • Ribonuclease III / genetics*
  • Urinary Bladder Neoplasms / genetics*


  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases

Supplementary concepts

  • Pleuropulmonary blastoma