DICER1 Mutations ID'd in Non-Epithelial Ovarian Cancer
Wednesday, December 21, 2011 (Last Updated: 12/22/2011)
WEDNESDAY, Dec. 21 (HealthDay News) -- Somatic missense mutations in the region of DICER1, which encodes the RNase IIIb domain, are common in nonepithelial ovarian tumors, according to a study published online Dec. 21 in the New England Journal of Medicine.
Alireza Heravi-Moussavi, Ph.D., from the University of British Columbia in Vancouver, Canada, and colleagues sequenced whole transcriptomes or exomes of 14 individuals with non-epithelial ovarian tumors to investigate the effect of somatic missense mutations of DICER1. Closely clustered mutations in the region of DICER1 were identified in four samples; and the region was further sequenced in additional ovarian and other tumors. In vitro RNA cleavage assays were carried out to investigate the effect of these mutations on the enzymatic activity of DICER1.
The investigators found that 29 percent of the non-epithelial ovarian tumors had DICER1 mutations in the RNase IIIb domain, including four tumors with additional germline DICER1 mutations. The mutations were mainly in Sertoli-Leydig cell tumors (60 percent). The mutations were somatic in all 16 samples with germline DNA available for testing, and were restricted to codons encoding metal-binding sites within the RNase IIIb catalytic centers. Mutations were also identified in non-seminomatous testicular germ-cell tumors (one of 14), embryonal rhabdomyosarcomas (two of five), and epithelial ovarian and endometrial carcinomas (one of 266). Mutant DICER1 proteins retained RNase IIIa activity but had reduced RNase IIIb activity.
"These mutations do not obliterate DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic," the authors write.
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