title: Combined comparative genomic hybridization and transcriptomic analyses of ovarian granulosa cell tumors point to novel candidate driver genes.
abstract: BACKGROUND
  Ovarian granulosa cell tumors (GCTs) are the most frequent sex cord-stromal tumors. Several studies have shown that a somatic mutation leading to a C134W substitution in the transcription factor FOXL2 appears in more than 95% of adult-type GCTs. Its pervasive presence suggests that FOXL2 is the main cancer driver gene. However, other mutations and genomic changes might also contribute to tumor formation and/or progression.
  
  
  METHODS
  We have performed a combined comparative genomic hybridization and transcriptomic analyses of 10 adult-type GCTs to obtain a picture of the genomic landscape of this cancer type and to identify new candidate co-driver genes.
  
  
  RESULTS
  Our results, along with a review of previous molecular studies, show the existence of highly recurrent chromosomal imbalances (especially, trisomy 14 and monosomy 22) and preferential co-occurrences (i.e. trisomy 14/monosomy 22 and trisomy 7/monosomy 16q). In-depth analyses showed the presence of recurrently broken, amplified/duplicated or deleted genes. Many of these genes, such as AKT1, RUNX1 and LIMA1, are known to be involved in cancer and related processes. Further genomic explorations suggest that they are functionally related.
  
  
  CONCLUSIONS
  Our combined analysis identifies potential candidate genes, whose alterations might contribute to adult-type GCT formation/progression together with the recurrent FOXL2 somatic mutation.
authors.affiliation: Institut Jacques Monod, Paris, France. caburet.sandrine@ijm.univ-paris-diderot.fr.|Université Paris Diderot/Paris, Paris, France. caburet.sandrine@ijm.univ-paris-diderot.fr.|Université Paris-Diderot & Institut Jacques Monod, CNRS-UMR 7592, Bâtiment Buffon, 15 Rue Hélène Brion, Paris, Cedex 13, France. caburet.sandrine@ijm.univ-paris-diderot.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Caburet
authors.affiliation: Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. mikko.anttonen@helsinki.fi.|Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. mikko.anttonen@helsinki.fi.
authors.forename: Mikko
authors.initials: M
authors.lastname: Anttonen
authors.affiliation: Institut Jacques Monod, Paris, France. todeschini@ijm.univ-paris-diderot.fr.|Université Paris Diderot/Paris, Paris, France. todeschini@ijm.univ-paris-diderot.fr.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Todeschini
authors.affiliation: Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. leila.unkila-kallio@hus.fi.
authors.forename: Leila
authors.initials: L
authors.lastname: Unkila-Kallio
authors.affiliation: Institut Jacques Monod, Paris, France. denis.mestivier@gmail.com.|Université Paris Diderot/Paris, Paris, France. denis.mestivier@gmail.com.
authors.forename: Denis
authors.initials: D
authors.lastname: Mestivier
authors.affiliation: Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. Ralf.Butzow@hus.fi.|Department of pathology, University of Helsinki, and HUSLAB, Helsinki University Central Hospital, Helsinki, Finland. Ralf.Butzow@hus.fi.
authors.forename: Ralf
authors.initials: R
authors.lastname: Butzow
authors.affiliation: Institut Jacques Monod, Paris, France. veitia.reiner@ijm.univ-paris-diderot.fr.|Université Paris Diderot/Paris, Paris, France. veitia.reiner@ijm.univ-paris-diderot.fr.|Université Paris-Diderot & Institut Jacques Monod, CNRS-UMR 7592, Bâtiment Buffon, 15 Rue Hélène Brion, Paris, Cedex 13, France. veitia.reiner@ijm.univ-paris-diderot.fr.
authors.forename: Reiner A
authors.initials: RA
authors.lastname: Veitia
mesh_terms: D055028:Comparative Genomic Hybridization; D050676:Core Binding Factor Alpha 2 Subunit / Q000096:biosynthesis / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D023281:Genomics; D006106:Granulosa Cell Tumor / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D017354:Point Mutation; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D003598:Cytoskeletal Proteins; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C403263:LIMA1 protein, human; D009363:Neoplasm Proteins; C493728:RUNX1 protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt