The gene expression signatures of melanoma progression

Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6092-7. doi: 10.1073/pnas.0501564102. Epub 2005 Apr 15.


Because of the paucity of available tissue, little information has previously been available regarding the gene expression profiles of primary melanomas. To understand the molecular basis of melanoma progression, we compared the gene expression profiles of a series of nevi, primary melanomas, and melanoma metastases. We found that metastatic melanomas exhibit two dichotomous patterns of gene expression, which unexpectedly reflect gene expression differences already apparent in comparing laser-capture microdissected radial and vertical phases of a large primary melanoma. Unsupervised hierarchical clustering accurately separated nevi and primary melanomas. Multiclass significance analysis of microarrays comparing normal skin, nevi, primary melanomas, and the two types of metastatic melanoma identified 2,602 transcripts that significantly correlated with sample class. These results suggest that melanoma pathogenesis can be understood as a series of distinct molecular events. The gene expression signatures identified here provide the basis for developing new diagnostics and targeting therapies for patients with malignant melanoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biopsy
  • Disease Progression
  • Gene Expression Profiling*
  • Humans
  • Immunohistochemistry
  • Melanoma / genetics*
  • Melanoma / pathology
  • Mutation
  • Neoplasm Metastasis / genetics
  • Nevus / genetics*
  • Nevus / pathology
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins B-raf / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / isolation & purification


  • RNA, Neoplasm
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf