title: Genome profiling of melanocytic tumors using multiplex ligation-dependent probe amplification (MLPA): Its usefulness as an adjunctive diagnostic tool for melanocytic tumors.
abstract: BACKGROUND
  The histopathology of melanocytic tumors sometimes presents diagnostic problems. Applicable parameters other than routine pathology are needed.
  
  
  OBJECTIVE
  We assessed the feasibility of multiplex ligation-dependent probe amplification (MLPA), a novel PCR-based genome profiling method, in the classification of melanocytic tumors.
  
  
  METHODS
  We extracted DNA from paraffin-embedded tissue sections of 24 primary melanomas, 14 Spitz nevi and 17 common melanocytic nevi. We analyzed the copy number gains or losses of a total of 76 genes spanning almost all chromosome arms using commercially available MLPA kits.
  
  
  RESULTS
  Although four melanocytic nevi and three Spitz nevi did not yield sufficient DNA for reliable analysis due to small tumor size, the MLPA analysis was feasible and applicable to the remaining 88% of samples. We found multiple genetic aberrations in primary melanomas. The total number of aberrations in each tumor ranged from 1 to 32 (average, 12.04). All but two melanomas showed aberrations at more than three genetic loci. Seventeen (70.8%) of the 24 melanomas showed a copy number loss of either the CDKN2A or CDKN2B gene on chromosome 9p21. All the Spitz nevi and 7 (50%) of 14 common melanocytic nevi had copy number changes at one or two gene loci (average, 1.04). The receiver operator characteristic curve analysis showed that the threshold value of copy number aberrations corresponding to 98% specificity for melanoma was 2.42 and the sensitivity using this threshold value was 92.5%.
  
  
  CONCLUSIONS
  MLPA could be used as an adjunctive diagnostic tool for melanocytic tumors.
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan. mtakata@hsp.md.shinshu-u.ac.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Takata
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ansai
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Kimura
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shirasaki
authors.forename: Naohito
authors.initials: N
authors.lastname: Hatta
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saida
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D019942:Genes, p16; D006801:Humans; D019656:Loss of Heterozygosity; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics; D015336:Molecular Probe Techniques; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D025521:Tumor Suppressor Proteins