title: Systematic classification of melanoma cells by phenotype-specific gene expression mapping.
abstract: There is growing evidence that the metastatic spread of melanoma is driven not by a linear increase in tumorigenic aggressiveness, but rather by switching back and forth between two different phenotypes of metastatic potential. In vitro these phenotypes are respectively defined by the characteristics of strong proliferation/weak invasiveness and weak proliferation/strong invasiveness. Melanoma cell phenotype is tightly linked to gene expression. Taking advantage of this, we have developed a gene expression-based tool for predicting phenotype called Heuristic Online Phenotype Prediction. We demonstrate the predictive utility of this tool by comparing phenotype-specific signatures with measurements of characteristics of melanoma phenotype-specific biology in different melanoma cell lines and short-term cultures. We further show that 86% of 536 tested melanoma lines and short-term cultures are significantly associated with the phenotypes we describe. These findings reinforce the concept that a two-state system, as described by the phenotype switching model, underlies melanoma progression.
authors.affiliation: Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Widmer
authors.forename: Phil F
authors.initials: PF
authors.lastname: Cheng
authors.forename: Ossia M
authors.initials: OM
authors.lastname: Eichhoff
authors.forename: Benedetta C
authors.initials: BC
authors.lastname: Belloni
authors.forename: Marie C
authors.initials: MC
authors.lastname: Zipser
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Schlegel
authors.forename: Delphine
authors.initials: D
authors.lastname: Javelaud
authors.forename: Alain
authors.initials: A
authors.lastname: Mauviel
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Keith S
authors.initials: KS
authors.lastname: Hoek
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D049109:Cell Proliferation; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D008545:Melanoma / Q000145:classification* / Q000235:genetics / Q000473:pathology; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness; D010641:Phenotype; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000145:classification
chemical_list: D014408:Biomarkers, Tumor