title: The gene expression signatures of melanoma progression.
abstract: 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.
authors.affiliation: 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
authors.forename: Christopher
authors.initials: C
authors.lastname: Haqq
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nosrati
authors.forename: Daniel
authors.initials: D
authors.lastname: Sudilovsky
authors.forename: Julia
authors.initials: J
authors.lastname: Crothers
authors.forename: Daniel
authors.initials: D
authors.lastname: Khodabakhsh
authors.forename: Brian L
authors.initials: BL
authors.lastname: Pulliam
authors.forename: Scot
authors.initials: S
authors.lastname: Federman
authors.forename: James R
authors.initials: JR
authors.lastname: Miller
authors.forename: Robert E
authors.initials: RE
authors.lastname: Allen
authors.forename: Mark I
authors.initials: MI
authors.lastname: Singer
authors.forename: Stanley P L
authors.initials: SP
authors.lastname: Leong
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Ljung
authors.forename: Richard W
authors.initials: RW
authors.lastname: Sagebiel
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kashani-Sabet
mesh_terms: 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
chemical_list: D012334:RNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf