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Dynamic Gene Expression Analysis Links Melanocyte Growth Arrest with Nevogenesis

¹ Wellman Center for Photomedicine, ² Division of Dermatopathology, and ³ Melanoma and Pigmented Lesion Center, Massachusetts General Hospital; ⁴ Harvard/Partners Center for Genetics and Genomics, Brigham and Women's Hospital, Boston, Massachusetts; and ⁵ Department of Dermatology, M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Hensin Tsao, Massachusetts General Hospital, Wellman Center for Photomedicine, Edwards 211, 55 Fruit Street, Boston, MA 02114-2696. Phone: 617-726-9569; Fax: 617-724-2745; E-mail: htsao{at}partners.org.

Like all primary cells in vitro, normal human melanocytes exhibit a physiologic decay in proliferative potential as it transitions to a growth-arrested state. The underlying transcriptional program(s) that regulate this phenotypic change is largely unknown. To identify molecular determinants of this process, we performed a Bayesian-based dynamic gene expression analysis on primary melanocytes undergoing proliferative arrest. This analysis revealed several related clusters whose expression behavior correlated with the melanocyte growth kinetics; we designated these clusters the melanocyte growth arrest program (MGAP). These MGAP genes were preferentially represented in benign melanocytic nevi over melanomas and selectively mapped to the hepatocyte fibrosis pathway. This transcriptional relationship between melanocyte growth stasis, nevus biology, and fibrogenic signaling was further validated in vivo by the demonstration of strong pericellular collagen deposition within benign nevi but not melanomas. Taken together, our study provides a novel view of fibroplasia in both melanocyte biology and nevogenesis. [Cancer Res 2009;69(23):OF1–9]

Key Words: Melanocyte • Expression Profiling • Nevus • Melanoma