title: Uveal melanoma hepatic metastases mutation spectrum analysis using targeted next-generation sequencing of 400 cancer genes.
abstract: OBJECTIVE
  Uveal melanoma (UM) is the most common malignant tumour of the eye. Diagnosis often occurs late in the course of disease, and prognosis is generally poor. Recently, recurrent somatic mutations were described, unravelling additional specific altered pathways in UM. Targeted next-generation sequencing (NGS) can now be applied to an accurate and fast identification of somatic mutations in cancer. The aim of the present study was to characterise the mutation pattern of five UM hepatic metastases with well-defined clinical and pathological features.
  
  
  METHODS
  We analysed the UM mutation spectrum using targeted NGS on 409 cancer genes.
  
  
  RESULTS
  Four previous reported genes were found to be recurrently mutated. All tumours presented mutually exclusive GNA11 or GNAQ missense mutations. BAP1 loss-of-function mutations were found in three UMs. SF3B1 missense mutations were found in the two UMs with no BAP1 mutations. We then searched for additional mutation targets. We identified the Arg505Cys mutation in the tumour suppressor FBXW7. The same mutation was previously described in different cancer types, and FBXW7 was recently reported to be mutated in UM exomes.
  
  
  CONCLUSIONS
  Further studies are required to confirm FBXW7 implication in UM tumorigenesis. Elucidating the molecular mechanisms underlying UM tumorigenesis holds the promise for novel and effective targeted UM therapies.
authors.affiliation: Service de Biochimie et de Génétique Moléculaire, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Luscan
authors.affiliation: INSERM, U1016, Institut Cochin, and CNRS, UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France Service d'Anatomie et Cytologie Pathologiques, AP-HP, Hôpital Cochin, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: P A
authors.initials: PA
authors.lastname: Just
authors.affiliation: Service de Biochimie et de Génétique Moléculaire, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Briand
authors.affiliation: Service de Biochimie et de Génétique Moléculaire, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Burin des Roziers
authors.affiliation: Service de Biochimie et de Génétique Moléculaire, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Goussard
authors.affiliation: Plateforme de Bioinformatique, Université Paris Descartes Sorbonne Paris Cité, Institut IMAGINE, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Nitschké
authors.affiliation: Service de Biochimie et de Génétique Moléculaire, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Vidaud
authors.affiliation: Institut Cochin-INSERM U1016, CNRS UMR 8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France APHP, Department of Dermatology, Cochin Hospital, Paris, France.
authors.forename: M F
authors.initials: MF
authors.lastname: Avril
authors.affiliation: INSERM, U1016, Institut Cochin, and CNRS, UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France Service d'Anatomie et Cytologie Pathologiques, AP-HP, Hôpital Cochin, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Terris
authors.affiliation: Service de Biochimie et de Génétique Moléculaire, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Pasmant
mesh_terms: D004252:DNA Mutational Analysis; D052138:Genes, Neoplasm / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary; D008545:Melanoma / Q000235:genetics* / Q000556:secondary; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics; D012189:Retrospective Studies; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins