Send to

Choose Destination
Int J Cancer. 2017 Nov 15;141(10):2030-2036. doi: 10.1002/ijc.30907. Epub 2017 Aug 21.

The prevalence of DICER1 pathogenic variation in population databases.

Author information

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Division of Pathology and Center for Genetic Medicine Research, Children's National Health System, Washington, DC.
Cancer and Blood Disorders, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN.
International Pleuropulmonary Blastoma Registry, Minneapolis, MN.
International Ovarian and Testicular Stromal Tumor Registry, Minneapolis, MN.
Department of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences, Washington, DC.


The DICER1 syndrome is associated with a variety of rare benign and malignant tumors, including pleuropulmonary blastoma (PPB), cystic nephroma (CN) and Sertoli-Leydig cell tumor (SLCT). The prevalence and penetrance of pathogenic DICER1 variation in the general population is unknown. We examined three publicly-available germline whole exome sequence datasets: Exome Aggregation Consortium (ExAC), 1,000 Genomes (1,000 G) and the Exome Sequencing Project (ESP). To avoid over-estimation of pathogenic DICER1 variation from cancer-associated exomes, we excluded The Cancer Genome Atlas (TCGA) variants from ExAC. All datasets were annotated with snpEff and ANNOVAR and variants were classified into four categories: likely benign (LB), unknown significance (VUS), likely pathogenic (LP), or pathogenic (P). The prevalence of DICER1 P/LP variants was 1:870 to 1:2,529 in ExAC-nonTCGA (53,105 exomes) estimated by metaSVM and REVEL/CADD, respectively. A more stringent prevalence calculation considering only loss-of-function and previously-published pathogenic variants detected in ExAC-nonTCGA, yielded a prevalence of 1:10,600. Despite the rarity of most DICER1 syndrome tumors, pathogenic DICER1 variation is more common than expected. If confirmed, these findings may inform future sequencing-based newborn screening programs for PPB, CN and SLCT, in which early detection improves prognosis.


DICER1; DICER1 syndrome; Sertoli-Leydig cell tumor; pleuropulmonary blastoma; prevalence estimates

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center