title: Whole-genome microarray detects deletions and loss of heterozygosity of chromosome 3 occurring exclusively in metastasizing uveal melanoma.
abstract: OBJECTIVE
  To detect deletions and loss of heterozygosity of chromosome 3 in a rare subset of fatal, disomy 3 uveal melanoma (UM), undetectable by fluorescence in situ hybridization (FISH).
  
  
  METHODS
  Multiplex ligation-dependent probe amplification (MLPA) with the P027 UM assay was performed on formalin-fixed, paraffin-embedded (FFPE) whole tumor sections from 19 disomy 3 metastasizing UMs. Whole-genome microarray analyses using a single-nucleotide polymorphism microarray (aSNP) were performed on frozen tissue samples from four fatal disomy 3 metastasizing UMs and three disomy 3 tumors with >5 years' metastasis-free survival.
  
  
  RESULTS
  Two metastasizing UMs that had been classified as disomy 3 by FISH analysis of a small tumor sample were found on MLPA analysis to show monosomy 3. No ubiquitous gene deletions of chromosome 3 were seen in the remaining 17 metastasizing disomy 3 UMs by MLPA. aSNP analysis revealed 95 deleted genes and 16 genes with loss of heterozygosity (LOH) on chromosome 3 in the disomy 3 metastasizing UMs that were not deleted or showing LOH in the nonmetastatic tumors.
  
  
  CONCLUSIONS
  MLPA can detect monosomy 3 cell populations in FFPE whole tumor sections previously missed by FISH performed on small tumor samples. Consistent deletion and LOH of genes on chromosome 3 occur in metastasizing disomy 3 UM and are detectable by aSNP analysis. Ninety-five genes were found to be deleted, and 16 genes showed LOH exclusively in disomy 3 metastasizing UM, suggesting a potential role for these genes in UM metastasis.
authors.affiliation: Pathology Department, School of Cancer Studies, University of Liverpool, Liverpool, UK. s.l.lake@liv.ac.uk
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Lake
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Coupland
authors.forename: Azzam F G
authors.initials: AF
authors.lastname: Taktak
authors.forename: Bertil E
authors.initials: BE
authors.lastname: Damato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015894:Genome, Human; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000556:secondary; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology