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Updated: May 7, 2026
12:42
Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression
Published on: August 28, 2012
Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers
Alireza Heravi-Moussavi1, Michael S Anglesio, S-W Grace Cheng
1British Columbia Cancer Research Centre, Vancouver, BC, Canada.
The New England Journal of Medicine
|December 23, 2011
Summary
Somatic DICER1 mutations in the RNase IIIb domain are common in nonepithelial ovarian tumors, particularly Sertoli-Leydig cell tumors. These mutations alter microRNA processing, contributing to oncogenesis.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Germline DICER1 mutations are linked to pleuropulmonary blastoma-family tumor and dysplasia syndrome.
- Mutation carriers have an increased risk of nonepithelial ovarian tumors, such as sex cord-stromal tumors.
Purpose of the Study:
- To investigate the role of DICER1 mutations in nonepithelial ovarian tumors.
- To determine the frequency and functional impact of DICER1 mutations in these tumors.
Main Methods:
- Whole transcriptome or exome sequencing of 14 nonepithelial ovarian tumors.
- Targeted sequencing of the DICER1 RNase IIIb domain in additional ovarian and other tumor types.
- In vitro RNA cleavage assays to assess mutant DICER1 enzymatic activity.
Main Results:
- DICER1 RNase IIIb domain mutations were found in 29% of 102 nonepithelial ovarian tumors, notably 60% of Sertoli-Leydig cell tumors.
- Mutations were somatic, located in metal-binding sites critical for microRNA processing, and reduced RNase IIIb activity while retaining RNase IIIa activity.
- Mutations were also detected in testicular germ-cell tumors, embryonal rhabdomyosarcomas, and rare epithelial ovarian/endometrial carcinomas.
Conclusions:
- Somatic DICER1 mutations in the RNase IIIb domain are a frequent event in nonepithelial ovarian tumors.
- These mutations partially impair DICER1 function, representing a novel oncogenic mechanism involving altered microRNA processing.
- The findings highlight a specific pathway through which microRNA dysregulation contributes to tumor development.
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