Germline DICER1 Mutations in Familial Pleuropulmonary Blastoma
By D. Hill, J. Ivanovich, J. Priest, C. Gurnett, L. Dehner, D. Desruisseau, J. Jarzembowski, K. Wikenheiser-Brokamp, B. Suarez, A. Whelan and 4 more. Science, 2009
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A rare form of lung cancer in children is associated with mutational disruption of an enzyme that generates small noncoding RNAs. Pleuropulmonary blastoma (PPB) is a rare pediatric lung tumor that is often part of an inherited cancer syndrome. PPBs consist of mesenchymal cells that are susceptible to malignant transformation and cysts lined by epithelial cells. In a subset of patients, overgrowth of the cysts by mesenchymal cells leads to sarcoma formation. Here, we show that 11 multiplex PPB families harbor heterozygous germline mutations in DICER1, a gene encoding an endoribonuclease critical to the generation of small noncoding regulatory RNAs. Expression of DICER1 protein was undetectable in the epithelial component of PPB tumors but was retained in the malignant mesenchyme (sarcoma). We hypothesize that loss of DICER1 in the epithelium of the developing lung alters the regulation of diffusible factors that promote mesenchymal proliferation.
Subfields: Pulmonary and Respiratory Medicine, Surgery
View Paper: https://www.semanticscholar.org/paper/7af72dfef26e096b18e52047cdbac04f145d01eb
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Citations in the corpus
- A census of human RNA-binding proteins (2014, background): “miRNAbinding cancer DICER1 pleuropulmonary blastoma, goiter with testicular tumors, embryonal habdomyosarcoma missense, nonsense mutation, frameshift (Foulkes et al., 2011; Hill et al., 2009; Rio Frio et al., 2011)”
- Non‐coding RNAs: regulators of disease (2010, background): “Likewise, a mutation resulting in premature termination of DICER1 results in pleuropulmonary blastoma, a rare paediatric lung tumour [163].”
- RNA-Binding Proteins in Cancer: Old Players and New Actors. (2017, background): “Mutations in the DICER1 gene impair miRNA-mediated gene suppression leading to DICER1 syndrome, an hereditary condition that predisposes patients to a variety of benign and malignant pediatric tumors, frequently including pleuropulmonary blastoma, cystic nephroma, multinodular goiter, and Sertoli–Le”