title: DICER1 and FOXL2 mutations in ovarian sex cord-stromal tumours: a GINECO Group study.
abstract: OBJECTIVE
  FOXL2 mutation has been consistently identified in adult granulosa cell tumours (A-GCTs). DICER1 mutations have been described predominantly in Sertoli-Leydig cell tumours (SLCTs). The prognostic implication of these mutations remains uncertain, as moderately sized studies have yielded variable outcomes. Our aim was to determine the implications of DICER1 and FOXL2 mutations in 156 ovarian sex cord-stromal tumours (SCSTs).
  
  
  RESULTS
  FOXL2 mutations were found in 94% of pathologically confirmed A-GCTs (95/101), in one of eight juvenile granulosa cell tumours (J-GCTs), and in two of 19 SLCTs. DICER1 mutations in the RNase IIIb domain were found in six of 19 SLCTs, two of eight J-GCTs, and one of 12 undifferentiated SCSTs (Und-SCSTs). Comparison of DICER1-mutated SLCTs with DICER1-non-mutated SLCTs showed that patient age at diagnosis was lower and oestrogen receptor expression was more frequent in DICER1-mutated tumours. With a median follow-up of 22 months, two of five DICER1-mutated SLCTs relapsed, in contrast to none of eight DICER1-non-mutated tumours.
  
  
  CONCLUSIONS
  Our results suggest that, in contrast to FOXL2 mutations in A-GCT, DICER1 mutations in SLCT might be more useful for prognosis than for diagnosis. However, study of a larger cohort of patients is necessary to establish this. Identification of genetic alterations in SCST offers promising therapeutic options.
authors.affiliation: U1052 Inserm, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Université de Lyon, Centre Léon Bérard, Lyon, France.|Institut Roche de Recherche et Médecine Translationnelle, Boulogne Billancourt, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Goulvent
authors.affiliation: Department of Medical Oncology, Université de Lyon, Centre Léon Bérard, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.affiliation: U1052 Inserm, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Université de Lyon, Centre Léon Bérard, Lyon, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Borel
authors.affiliation: Pathology Department, Centre Léon Bérard, Lyon, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Haddad
authors.affiliation: Pathology Department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Devouassoux-Shisheboran
authors.affiliation: Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Marie-Cecile
authors.initials: MC
authors.lastname: Vacher-Lavenu
authors.affiliation: Hôtel-Dieu, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Laurraine
authors.affiliation: RocheSAS Scientific Partnerships, Boulogne Billancourt, France.
authors.forename: Ariel
authors.initials: A
authors.lastname: Savina
authors.affiliation: Department of Medical Oncology, Université de Lyon, Centre Léon Bérard, Lyon, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Maillet
authors.affiliation: U1052 Inserm, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Université de Lyon, Centre Léon Bérard, Lyon, France.
authors.forename: Germain
authors.initials: G
authors.lastname: Gillet
authors.affiliation: Pathology Department, Centre Léon Bérard, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Treilleux
authors.affiliation: U1052 Inserm, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Université de Lyon, Centre Léon Bérard, Lyon, France.
authors.forename: Ruth
authors.initials: R
authors.lastname: Rimokh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D000074842:Forkhead Box Protein L2 / Q000235:genetics*; D006106:Granulosa Cell Tumor / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016612:Paraffin Embedding; D011379:Prognosis; D043244:Ribonuclease III / Q000235:genetics*; D018310:Sertoli-Leydig Cell Tumor / Q000235:genetics* / Q000473:pathology; D018312:Sex Cord-Gonadal Stromal Tumors / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: DICER1; FOXL2; ovary; sex cord-stromal tumours