DICER1 mutations in familial pleuropulmonary blastoma. Science 2009 Aug 21;325(5943):965
Date
06/27/2009Pubmed ID
19556464Pubmed Central ID
PMC3098036DOI
10.1126/science.1174334Scopus ID
2-s2.0-67749129007 (requires institutional sign-in at Scopus site) 562 CitationsAbstract
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.
Author List
Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJAuthor
Jason A. Jarzembowski MD, PhD Sr Associate Dean, CEO CSG, Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
DEAD-box RNA HelicasesEpithelium
Female
Genetic Predisposition to Disease
Germ-Line Mutation
Heterozygote
Humans
Lung Neoplasms
Male
Pedigree
Pulmonary Blastoma
Ribonuclease III
