title: High-Resolution Array CGH Analysis Identifies Regional Deletions and Amplifications of Chromosome 8 in Uveal Melanoma.
abstract: OBJECTIVE
  Monosomy 3 (M3) and abnormalities of chromosome 8 associate with poor prognosis in uveal melanomas (UM). Although M3 has been the subject of more in-depth studies, none have intensively focused on chromosome 8. To elucidate the potential role of chromosome 8 abnormalities, array comparative genomic hybridization (aCGH) was performed on primary UM.
  
  
  METHODS
  A specifically-designed custom high-resolution array was developed focusing on changes most implicated in UM. Probes for chromosome 8 had a mean spacing of 2.3 kb while chromosomes infrequently affected had a mean spacing of 36.6 kb. A series of 75 UM, including one formalin-fixed paraffin sample were analyzed, and where possible control DNA extracted from the patient's own peripheral blood was used.
  
  
  RESULTS
  The most common copy number abnormalities were chromosome 8 (75%) and M3 (51%), with M3 and gain of the long arm of chromosome 8 (8q+) associated in 41% of cases. Also identified were partial deletions of chromosome 3 (3%) and regional 8q+ (23%), and the intensive coverage of chromosome 8 revealed small focal deletions and amplifications affecting both arms. The most significant predictor of prognosis was M3/8q+ having a hazard ratio of 10.1 (P < 0.0001).
  
  
  CONCLUSIONS
  Neither 8p deletion nor focal changes affecting chromosome 8 were linked to outcome. The most significant indicator was M3/8q, and multiple 8q+ associated with shorter survival. Studying UM with this technology provides a powerful robust tool for predicting prognosis while considering other genetic changes, allowing the future incorporation of such data as it becomes clinically significant.
authors.affiliation: Academic Unit of Ophthalmology and Orthoptics Department of Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Hammond
authors.affiliation: Academic Unit of Ophthalmology and Orthoptics Department of Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom 2Pathology and Clinical Laboratory, King Fahad Medical City, R.
authors.forename: Nawal S D
authors.initials: NS
authors.lastname: Al-Shammari
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Danson
authors.affiliation: Sheffield Ocular Oncology Service, Sheffield Teaching Hospitals, Royal Hallamshire Hospital, Sheffield, United Kingdom.
authors.forename: Rhona
authors.initials: R
authors.lastname: Jacques
authors.affiliation: Academic Unit of Ophthalmology and Orthoptics Department of Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom 4Sheffield Ocular Oncology Service, Sheffield Teaching Hospita.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Rennie
authors.affiliation: Academic Unit of Ophthalmology and Orthoptics Department of Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Sisley
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D005260:Female; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D009006:Monosomy / Q000235:genetics; D012044:Regression Analysis; D017384:Sequence Deletion; D016019:Survival Analysis; D014604:Uveal Neoplasms / Q000235:genetics*; D055815:Young Adult; D000098943:Uveal Melanoma