title: DICER1 mutations in familial pleuropulmonary blastoma.
abstract: 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.
authors: Washington University Medical Center, St. Louis, MO 63110, USA. dashill@cnmc.org
authors: D Ashley
authors: DA
authors: Hill
authors: Jennifer
authors: J
authors: Ivanovich
authors: John R
authors: JR
authors: Priest
authors: Christina A
authors: CA
authors: Gurnett
authors: Louis P
authors: LP
authors: Dehner
authors: David
authors: D
authors: Desruisseau
authors: Jason A
authors: JA
authors: Jarzembowski
authors: Kathryn A
authors: KA
authors: Wikenheiser-Brokamp
authors: Brian K
authors: BK
authors: Suarez
authors: Alison J
authors: AJ
authors: Whelan
authors: Gretchen
authors: G
authors: Williams
authors: Dawn
authors: D
authors: Bracamontes
authors: Yoav
authors: Y
authors: Messinger
authors: Paul J
authors: PJ
authors: Goodfellow
mesh_terms: D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D010375:Pedigree; D018202:Pulmonary Blastoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D043244:Ribonuclease III / Q000737:chemistry / Q000235:genetics*
chemical_list: C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases