Genetics and Genomics

BJC Open article

British Journal of Cancer (2013) 109, 2744–2750. doi:10.1038/bjc.2013.637
Published online 17 October 2013

DICER1 hotspot mutations in non-epithelial gonadal tumours

L Witkowski1,2,3, J Mattina2, S Schönberger4, M J Murray5,6, D G Huntsman7, J S Reis-Filho8, W G McCluggage9, J C Nicholson5, N Coleman6, G Calaminus10, D T Schneider11, J Arseneau12, C J R Stewart13 and W D Foulkes1,2,3,14

  1. 1Department of Oncology and Human Genetics, Program in Cancer Genetics, McGill University, Montreal, Quebec, Canada
  2. 2Department of Medical Genetics, Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
  3. 3Department of Human Genetics, McGill University, Montreal, Quebec, Canada
  4. 4Department of Paediatric Haematology and Oncology, University of Bonn, University Children’s Hospital, Bonn, Germany
  5. 5Department of Paediatric Oncology and Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  6. 6Department of Pathology, University of Cambridge, Cambridge, UK
  7. 7Departments of Pathology, Vancouver General Hospital, Centre for Translational and applied Genomics, the British Columbia Cancer Agency and the Genetic Pathology Evaluation Centre, Vancouver, British Columbia, Canada
  8. 8Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
  9. 9Department of Pathology, Royal Group of Hospitals Trust, Belfast, UK
  10. 10Department of Paediatric Haematology and Oncology, University of Münster, Münster, Germany
  11. 11Clinic of Paediatrics, Municipal Hospital Dortmund, Dortmund, Germany
  12. 12Department of Pathology, McGill University, Montreal, Quebec, Canada
  13. 13Department of Histopathology, King Edward Memorial Hospital, Perth, Australia
  14. 14Department of Medical Genetics, Research Institute, McGill University Health Centre, Montreal, Quebec, Canada

Correspondence: Dr WD Foulkes, E-mail:

Received 6 June 2013; Revised 22 September 2013; Accepted 23 September 2013
Advance online publication 17 October 2013





Non-epithelial gonadal tumours largely comprise sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Specific somatic mutations in DICER1, a microRNA maturation pathway gene, have been identified in these tumours. We conducted a study that aimed to confirm, refine and extend the previous observations.



We used Sanger sequencing to sequence the RNase IIIa and IIIb domains of DICER1 in 154 gonadal tumours from 135 females and 19 males, as well as 43 extra-gonadal GCTs from 26 females and 17 males.



We identified heterozygous non-synonymous mutations in the RNase IIIb domain of DICER1 in 14/197 non-epithelial tumours (7.1%). Mutations were found in 9/28 SCSTs (32%), 5/118 gonadal GCTs (4.2%), 0/43 extra-gonadal GCTs and 0/8 miscellaneous tumours. The 14 mutations affected only five residues: E1705, D1709, E1788, D1810 and E1813. In all five patients where matched and constitutional DNA was available, the mutations were only somatic. There were no mutations found in the RNase IIIa domain.



More than half (8/15) of Sertoli–Leydig cell tumours (SLCTs) harbour DICER1 mutations in the RNase IIIb domain, while mutations are rarely found in GCTs. Genetic alterations in SLCTs may aid in classification and provide new approaches to therapy.


DICER1; germ cell tumours; sex cord-stromal tumours; ovarian; testicular; microRNA