title: Genome-wide profiling is a clinically relevant and affordable prognostic test in posterior uveal melanoma.
abstract: OBJECTIVE
  This study investigated the capacity of genetic analysis of uveal melanoma samples to identify high-risk patients and discusses its clinical implications.
  
  
  METHODS
  Patients with posterior uveal melanoma were prospectively enrolled. Tumour samples were derived from enucleated globe, fine-needle aspirates or endoresection. Chromosome 3 and 8 status was determined by array comparative genomic hybridisation (array-CGH). Patients were followed after treatment to detect metastasis.
  
  
  RESULTS
  Four groups were classified by array-CGH. Patients were divided into disomy 3 and normal chromosome 8 (D3/8nl), disomy 3 and 8q gain (D3/8g), monosomy 3 and normal chromosome 8 (M3/8nl) and monosomy 3 and 8 or 8q gain (M3/8g). Median follow-up was 28 months (range: 1-147 months). At the end of the study, 128 patients (33.7%) had developed metastasis and 96 patients had died. Univariate Cox proportional hazard analysis showed that factors associated with metastasis included basal tumour diameter p=0.0007, tumour thickness p=0.01, mixed/epithelioid cell type p=0.0009 and genomic data p<0.0001. High-risk profile was more strongly associated with metastasis than the other prognostic factors p<0.001. Multivariate Cox modelling analysis showed that the status of chromosomes 3 and 8 were the only two variables that independently contributed to prognosis: monosomy 3 alone p=0.001 and monosomy 3 and 8q gain p<0.0001.
  
  
  CONCLUSIONS
  Array-CGH allowed identification of three prognostic groups with low, intermediate and high risk of developing metastasis. Array-CGH is a reliable and inexpensive method for uveal melanoma prognosis. This method is now currently used in France.
authors.affiliation: Department of Surgical Oncology, Institut Curie 26 rue d'Ulm, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cassoux
authors.affiliation: Department of Medical Oncology, Institut Curie 26 rue d'Ulm, Paris, France.
authors.forename: Manuel Jorge
authors.initials: MJ
authors.lastname: Rodrigues
authors.affiliation: Department of Biostatistics, Institut Curie 25 rue d'Ulm, Paris, France.
authors.forename: Corine
authors.initials: C
authors.lastname: Plancher
authors.affiliation: Department of Biostatistics, Institut Curie 25 rue d'Ulm, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.affiliation: Department of Surgical Oncology, Institut Curie 26 rue d'Ulm, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Levy-Gabriel
authors.affiliation: Department of Surgical Oncology, Institut Curie 26 rue d'Ulm, Paris, France.
authors.forename: Livia
authors.initials: L
authors.lastname: Lumbroso-Le Rouic
authors.affiliation: Department of Medical Oncology, Institut Curie 26 rue d'Ulm, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Piperno-Neumann
authors.affiliation: Department of Radiotherapy Orsay Proton therapy, Center Institut Curie Orsay, Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Dendale
authors.affiliation: Department of Pathology, Institut Curie 25 rue d'Ulm, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre
authors.affiliation: Department of Surgical Oncology, Institut Curie 26 rue d'Ulm, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Desjardins
authors.affiliation: Department of Genetics, Institut Curie 25 rue d'Ulm, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D009006:Monosomy; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D014604:Uveal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary; D055815:Young Adult; D000098943:Uveal Melanoma
keywords: Choroid; Diagnostic tests/Investigation; Genetics; Pathology