Molecular classification of cutaneous malignant melanoma by gene expression profiling

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Abstract
The most common human cancers are malignant neoplasms of the skin1,2. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease3,4. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm2,3. Accordingly, though melanoma is thought to present with different ‘taxonomic’ forms, these are considered part of a continuous spectrum rather than discrete entities2. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas5. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.