The gene expression signatures of melanoma progression.
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.
Haqq
Christopher
C
Auerback Melanoma Research Laboratory, Melanoma Center and Department of Dermatology, Cutaneous Oncology Program, University of California at San Francisco (UCSF) Comprehensive Cancer Center, San Francisco, CA 94115, USA. chaqq@itsa.ucsf.edu
Nosrati
Mehdi
M
Sudilovsky
Daniel
D
Crothers
Julia
J
Khodabakhsh
Daniel
D
Pulliam
Brian L
BL
Federman
Scot
S
Miller
James R
JR
Allen
Robert E
RE
Singer
Mark I
MI
Leong
Stanley P L
SP
Ljung
Britt-Marie
BM
Sagebiel
Richard W
RW
Kashani-Sabet
Mohammed
M
D001706:Biopsy; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics; D009506:Nevus / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification
D012334:RNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf