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Uveal melanoma hepatic metastases mutation spectrum analysis using targeted next-generation sequencing of 400 cancer genes
  1. A Luscan1,2,
  2. P A Just3,4,
  3. A Briand1,2,
  4. C Burin des Roziers1,
  5. P Goussard1,
  6. P Nitschké5,
  7. M Vidaud1,2,
  8. M F Avril6,7,
  9. B Terris3,4,
  10. E Pasmant1,2
  1. 1Service de Biochimie et de Génétique Moléculaire, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France
  2. 2EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France
  3. 3INSERM, U1016, Institut Cochin, and CNRS, UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France
  4. 4Service d'Anatomie et Cytologie Pathologiques, AP-HP, Hôpital Cochin, Université Paris Descartes Sorbonne Paris Cité, Paris, France
  5. 5Plateforme de Bioinformatique, Université Paris Descartes Sorbonne Paris Cité, Institut IMAGINE, Paris, France
  6. 6Institut Cochin—INSERM U1016, CNRS UMR 8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France
  7. 7APHP, Department of Dermatology, Cochin Hospital, Paris, France
  1. Correspondence to Dr Eric Pasmant, Service de Biochimie et de Génétique Moléculaire, Hôpital Cochin, AP-HP, Bâtiment Jean DAUSSET—3ème étage, 27 rue du Faubourg Saint Jacques, Paris 75006, France; eric.pasmant{at}


Aims 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.

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