Published in: Nature, vol. 406, no. 6795, pp. 536-540 (August 3, 2000):

"Molecular Classification of Cutaneous Malignant Melanoma by Gene Expression Profiling". 

M. Bittner*, X, P. Meltzer*, X, Y. Chen*, Y. Jiang*, E. Seftor³, M. Hendrix³, M. Radmacher§, R. Simon§, Z. Yakhini k, A. Ben-Dork¶, N. Sampas k, E. Dougherty#, E. Wang I , F. Marincola I , C. Gooden*, J. Lueders*, A. Glatfelter*, P. Pollock**, J. Carpten*, E. Gillanders*, D. Leja*, K. Dietrich*, C. Beaudry²², M. Berens²², D. Alberts³³, V. Sondak§§, N. Hayward** & J. Trent*

*Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA
³ Department of Anatomy and Cell Biology, University of Iowa Cancer Center, Iowa City, Iowa 52242-1109, USA
§ National Cancer Institute, DCTDC, NIH, Bethesda, Maryland 20852, USA
k Chemical and Biological Systems Department, Agilent Laboratories, 3500 Deer Creek Road, Palo Alto, California 94304, USA
¶ Computer Science and Engineering Department, University of Washington, Seattle, Washington 98105, USA
# Department of Electrical Engineering, Texas A & M University, College Station, Texas 77843, USA
I National Cancer Institute, Surgery Branch, NIH, Bethesda, Maryland 20850, USA
** Queensland Institute of Medical Research, Herston, Queensland 4029, Australia
²² Neuro-Oncology Laboratory, Barrow Neurological Institute, Phoenix, Arizona 85013-4496, USA
³³ Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA
§§ Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA
 X These authors contributed equally to this work. 


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The most common human cancers are malignant neoplasms of the skin [1,2] . Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease [3,4] . Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm [2,3] . Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities [2] . 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 melanomas [5] . Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

References Cited:

1. Hall, H. I., Miller, D. R., Rogers, J. D. & Bewerse, B. Update on the incidence and mortality from melanoma in the United States. J. Am. Acad. Dermatol. 40, 35-42 (1999).

2. Weyers, W., Euler, M., Diaz-Cascajo, C., Schill, W. B. & Bonczkowitz, M. Classification of cutaneous malignant melanoma: a reassessment of histopathologic criteria for the distinction of different types. Cancer 86, 288-299 (1999).

3. Byers, H. R. & Bhawan, J. Pathologic parameters in the diagnosis and prognosis of primary cutaneous melanoma. Hematol. Oncol. Clin. North Am. 12, 717-735 (1998).

4. McMasters, K. M., Sondak, V. K., Lotze, M. T. & Ross, M. I. Recent advances in melanoma staging and therapy. Ann. Surg. Oncol. 6, 467-475, (1999).

5. Maniotis, A. J. et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am. J. Pathol. 155, 739-752 (1999).

6. DeRisi, J. et al. Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nature Genet. 14, 457-460 (1996).

7. Khan, J. et al. Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays. Cancer Res. 58, 5009-5013 (1998)

8. Perou, C. M. et al. Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc. Natl Acad. Sci. USA 96, 9212-9217 (1999).

9. Golub, T. R. et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286, 531-537, (1999).

10. Alizadeh, A. et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403, 503-511 (2000).


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

Additional References:


1. "Mated Models of Gene Regulation in Eukaryotes".

2. "Oncogenes as Molecular Targets within Active Chromatin".


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