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Letters to Nature

Nature 406, 536-540 (3 August 2000) | doi:10.1038/35020115; Received 12 January 2000; Accepted 16 May 2000

Open Innovation Challenges

Molecular classification of cutaneous malignant melanoma by gene expression profiling

M. Bittner1,2, P. Meltzer1,2, Y. Chen1, Y. Jiang1, E. Seftor3, M. Hendrix3, M. Radmacher4, R. Simon4, Z. Yakhini5, A. Ben-Dor5,6, N. Sampas5, E. Dougherty7, E. Wang8, F. Marincola8, C. Gooden1, J. Lueders1, A. Glatfelter1, P. Pollock9, J. Carpten1, E. Gillanders1, D. Leja1, K. Dietrich1, C. Beaudry10, M. Berens10, D. Alberts11, V. Sondak12, N. Hayward9 & J. Trent1

  1. Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA
  2. Department of Anatomy and Cell Biology, University of Iowa Cancer Center, Iowa City, Iowa 52242-1109, USA
  3. National Cancer Institute, DCTDC, NIH, Bethesda, Maryland 20852, USA
  4. Chemical and Biological Systems Department, Agilent Laboratories, 3500 Deer Creek Road, Palo Alto, California 94304, USA
  5. Computer Science and Engineering Department, University of Washington, Seattle, Washington 98105, USA
  6. Department of Electrical Engineering, Texas A & M University, College Station, Texas 77843, USA
  7. National Cancer Institute, Surgery Branch, NIH, Bethesda, Maryland 20850, USA
  8. Queensland Institute of Medical Research , Herston, Queensland 4029, Australia
  9. Neuro-Oncology Laboratory, Barrow Neurological Institute, Phoenix, Arizona 85013-4496 , USA
  10. Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA
  11. Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA
  12. These authors contributed equally to this work.

Correspondence to: M. Bittner1,2 Correspondence and requests for materials should be addressed to J.T. (Email: jtrent@nih.gov) or M.B. (Email: mbittner@nhgri.nih.gov ).

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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.