title: Gene expression signatures for tumor progression, tumor subtype, and tumor thickness in laser-microdissected melanoma tissues.
abstract: OBJECTIVE
  To better understand the molecular mechanisms of malignant melanoma progression and metastasis, gene expression profiling was done of primary melanomas and melanoma metastases.
  
  
  METHODS
  Tumor cell-specific gene expression in 19 primary melanomas and 22 melanoma metastases was analyzed using oligonucleotide microarrays after laser-capture microdissection of melanoma cells. Statistical analysis was done by random permutation analysis and support vector machines. Microarray data were further validated by immunohistochemistry and immunoblotting.
  
  
  RESULTS
  Overall, 308 genes were identified that showed significant differential expression between primary melanomas and melanoma metastases (false discovery rate<or=0.05). Significantly overrepresented gene ontology categories in the list of 308 genes were cell cycle regulation, mitosis, cell communication, and cell adhesion. Overall, 47 genes showed up-regulation in metastases. These included Cdc6, Cdk1, septin 6, mitosin, kinesin family member 2C, osteopontin, and fibronectin. Down-regulated genes included E-cadherin, fibroblast growth factor binding protein, and desmocollin 1 and desmocollin 3, stratifin/14-3-3sigma, and the chemokine CCL27. Using support vector machine analysis of gene expression data, a performance of >85% correct classifications for primary melanomas and metastases was reached. Further analysis showed that subtypes of primary melanomas displayed characteristic gene expression patterns, as do thin tumors (<or=1.0 mm Breslow thickness) compared with intermediate and thick tumors (>2.0 mm Breslow thickness).
  
  
  CONCLUSIONS
  Taken together, this large-scale gene expression study of malignant melanoma identified molecular signatures related to metastasis, melanoma subtypes, and tumor thickness. These findings not only provide deeper insights into the pathogenesis of melanoma progression but may also guide future research on innovative treatments.
authors.affiliation: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Jaeger
authors.forename: Dirk
authors.initials: D
authors.lastname: Koczan
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Thiesen
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Ibrahim
authors.forename: Gerd
authors.initials: G
authors.lastname: Gross
authors.forename: Rainer
authors.initials: R
authors.lastname: Spang
authors.forename: Manfred
authors.initials: M
authors.lastname: Kunz
mesh_terms: D002448:Cell Adhesion; D002450:Cell Communication; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry
chemical_list: D009841:Oligonucleotides