title: Dynamic gene expression analysis links melanocyte growth arrest with nevogenesis.
abstract: 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.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital Boston, Massachusetts 02114-2696, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Khanh
authors.initials: K
authors.lastname: Thieu
authors.forename: Kenneth Y
authors.initials: KY
authors.lastname: Tsai
authors.forename: Adriano
authors.initials: A
authors.lastname: Piris
authors.forename: Durga
authors.initials: D
authors.lastname: Udayakumar
authors.forename: Ching-Ni Jenny
authors.initials: CN
authors.lastname: Njauw
authors.forename: Marco F
authors.initials: MF
authors.lastname: Ramoni
authors.forename: Hensin
authors.initials: H
authors.lastname: Tsao
mesh_terms: D001499:Bayes Theorem; D048708:Cell Growth Processes / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000502:physiology*; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009506:Nevus / Q000235:genetics* / Q000473:pathology