title: DICER1 hotspot mutations in non-epithelial gonadal tumours.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1] Department of Oncology and Human Genetics, Program in Cancer Genetics, McGill University, Montreal, Quebec, Canada [2] Department of Medical Genetics, Lady Davis Institute and Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, Quebec, Canada [3] Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Witkowski
authors.forename: J
authors.initials: J
authors.lastname: Mattina
authors.forename: S
authors.initials: S
authors.lastname: Schönberger
authors.forename: M J
authors.initials: MJ
authors.lastname: Murray
authors.forename: C S
authors.initials: CS
authors.lastname: Choong
authors.forename: D G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: J S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: W G
authors.initials: WG
authors.lastname: McCluggage
authors.forename: J C
authors.initials: JC
authors.lastname: Nicholson
authors.forename: N
authors.initials: N
authors.lastname: Coleman
authors.forename: G
authors.initials: G
authors.lastname: Calaminus
authors.forename: D T
authors.initials: DT
authors.lastname: Schneider
authors.forename: J
authors.initials: J
authors.lastname: Arseneau
authors.forename: C J R
authors.initials: CJ
authors.lastname: Stewart
authors.forename: W D
authors.initials: WD
authors.lastname: Foulkes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009373:Neoplasms, Germ Cell and Embryonal / Q000453:epidemiology / Q000235:genetics; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics*; D018312:Sex Cord-Gonadal Stromal Tumors / Q000453:epidemiology / Q000235:genetics*; D013736:Testicular Neoplasms / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases