Sequencing of DICER1 in sarcomas identifies biallelic somatic DICER1 mutations in an adult-onset embryonal rhabdomyosarcoma

Br J Cancer. 2017 Jun 6;116(12):1621-1626. doi: 10.1038/bjc.2017.147. Epub 2017 May 18.


Background: Sarcomas are rare and heterogeneous cancers. We assessed the contribution of DICER1 mutations to sarcoma development.

Methods: The coding region of DICER1 was sequenced in 67 sarcomas using a custom Fluidigm Access Array. The RNase III domains were Sanger sequenced in six additional sarcomas to identify hotspot DICER1 variants.

Results: The median age of sarcoma diagnosis was 45.7 years (range: 3 months to 87.4 years). A recurrent embryonal rhabdomyosarcoma (ERMS) of the broad ligament, first diagnosed at age 23 years, harboured biallelic pathogenic somatic DICER1 variants (1 truncating and 1 RNase IIIb missense). We identified nine other DICER1 variants. One somatic variant (p.L1070V) identified in a pleomorphic sarcoma and one germline variant (c.2257-7A>G) may be pathogenic, but the others are considered to be benign.

Conclusions: We show that deleterious DICER1 mutations underlie the genetic basis of only a small fraction of sarcomas, in particular ERMS of the urogenital tract.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alleles
  • Child
  • Child, Preschool
  • DEAD-box RNA Helicases / genetics*
  • DNA Mutational Analysis
  • DNA, Neoplasm / analysis*
  • Female
  • Germ-Line Mutation
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Rhabdomyosarcoma, Embryonal / genetics*
  • Ribonuclease III / genetics*
  • Sarcoma, Ewing / genetics*
  • Young Adult


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