@article{d93902148aa4421092b4445bfd63cf60,
title = "A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation",
abstract = "The {"}cancerized field{"} concept posits that cancer-prone cells in a given tissue share an oncogenic mutation, but only discreet clones within the field initiate tumors. Most benign nevi carry oncogenic BRAFV600E mutations but rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors (NCPs) and specifically reexpressed in melanoma. Live imaging of transgenic zebrafish crestin reporters shows that within a cancerized field (BRAFV600E -mutant; p53-deficient), a single melanocyte reactivates the NCP state, revealing a fate change at melanoma initiation in this model. NCP transcription factors, including sox10, regulate crestin expression. Forced sox10 overexpression in melanocytes accelerated melanoma formation, which is consistent with activation of NCP genes and super-enhancers leading to melanoma. Our work highlights NCP state reemergence as a key event in melanoma initiation.",
author = "Kaufman, {Charles K.} and Christian Mosimann and Fan, {Zi Peng} and Song Yang and Thomas, {Andrew J.} and Julien Ablain and Tan, {Justin L.} and Fogley, {Rachel D.} and {Van Rooijen}, Ellen and Hagedorn, {Elliott J.} and Christie Ciarlo and White, {Richard M.} and Matos, {Dominick A.} and Puller, {Ann Christin} and Cristina Santoriello and Liao, {Eric C.} and Young, {Richard A.} and Zon, {Leonard I.}",
note = "Funding Information: C.K.K. and research reported here is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award K08 AR061071. C.M. received support from a European Molecular Biology Organization long-term fellowship, a Human Frontier Science Program long-term fellowship, and a Swiss National Science Foundation advanced postdoctoral fellowship. L.I.Z. is supported by R01 CA103846, the Ellison Foundation, the V Foundation, and the Melanoma Research Alliance and is a Howard Hughes Medical Institute Investigator. R.A.Y. is supported by NIH HG002668. Z.P.F. was supported by NIH HG002668. E.J.H. is a Howard Hughes Medical Institute Fellow of the Helen Hay Whitney Foundation. L.I.Z. is a founder and stock holder of Fate, Inc. and Scholar Rock. R.A.Y. is a founder of Syros Pharmaceuticals. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank the Massachusetts General Hospital DNA Core for providing technical assistance with deep sequencing. We thank J. Ablain for critical review of the manuscript, C. Ceol for the gift of the zebrafish mitfa middle entry clone, and G. Musso for helpful discussions on microarray data and GSEA. All microarray, Chip-seq, and RNA-seq are deposited at Gene Expression Omnibus, ID GSE75356.",
year = "2016",
month = jan,
day = "29",
doi = "10.1126/science.aad2197",
language = "English",
volume = "351",
pages = "464 and aad21971--aad219710",
journal = "Science",
issn = "0036-8075",
number = "6272",
}