Publication Date:
2009-06-27
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098036/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098036/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hill, D Ashley -- Ivanovich, Jennifer -- Priest, John R -- Gurnett, Christina A -- Dehner, Louis P -- Desruisseau, David -- Jarzembowski, Jason A -- Wikenheiser-Brokamp, Kathryn A -- Suarez, Brian K -- Whelan, Alison J -- Williams, Gretchen -- Bracamontes, Dawn -- Messinger, Yoav -- Goodfellow, Paul J -- P30 CA091842/CA/NCI NIH HHS/ -- P30 CA091842-07/CA/NCI NIH HHS/ -- P30 CA091842-08/CA/NCI NIH HHS/ -- R01 CA143167/CA/NCI NIH HHS/ -- R01 HL109265/HL/NHLBI NIH HHS/ -- UL1 RR024992/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 21;325(5943):965. doi: 10.1126/science.1174334. Epub 2009 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Washington University Medical Center, St. Louis, MO 63110, USA. dashill@cnmc.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556464" target="_blank"〉PubMed〈/a〉
Keywords:
DEAD-box RNA Helicases/chemistry/*genetics
;
Epithelium/metabolism
;
Female
;
Genetic Predisposition to Disease
;
*Germ-Line Mutation
;
Heterozygote
;
Humans
;
Lung Neoplasms/enzymology/*genetics/pathology
;
Male
;
Pedigree
;
Pulmonary Blastoma/enzymology/*genetics/pathology
;
Ribonuclease III/chemistry/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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