Biallelic DICER1 mutations in sporadic pleuropulmonary blastoma

Cancer Res. 2014 May 15;74(10):2742-9. doi: 10.1158/0008-5472.CAN-13-2470. Epub 2014 Mar 27.


Pleuropulmonary blastoma (PPB) is a rare pediatric malignancy whose pathogens are poorly understood. Recent reports suggest that germline mutations in the microRNA-processing enzyme DICER1 may contribute to PPB development. To investigate the genetic basis of this cancer, we performed whole-exome sequencing or targeted deep sequencing of multiple cases of PPB. We found biallelic DICER1 mutations to be very common, more common than TP53 mutations also found in many tumors. Somatic ribonuclease III (RNase IIIb) domain mutations were identified in all evaluable cases, either in the presence or absence of nonsense/frameshift mutations. Most cases had mutated DICER1 alleles in the germline with or without an additional somatic mutation in the remaining allele, whereas other cases displayed somatic mutations exclusively where the RNase IIIb domain was invariably affected. Our results highlight the role of RNase IIIb domain mutations in DICER1 along with TP53 inactivation in PPB pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • DEAD-box RNA Helicases / genetics*
  • DNA Mutational Analysis
  • Exome
  • Gene Frequency
  • Germ-Line Mutation*
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Paraffin Embedding
  • Polymorphism, Single Nucleotide
  • Pulmonary Blastoma / enzymology
  • Pulmonary Blastoma / genetics*
  • Ribonuclease III / genetics*
  • Tumor Suppressor Protein p53 / genetics


  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases