PUBLICATION

A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation

Authors
Kaufman, C.K., Mosimann, C., Fan, Z.P., Yang, S., Thomas, A.J., Ablain, J., Tan, J.L., Fogley, R.D., van Rooijen, E., Hagedorn, E.J., Ciarlo, C., White, R.M., Matos, D.A , Puller, A.C., Santoriello, C., Liao, E.C., Young, R.A., and Zon, L.I.
ID
ZDB-PUB-160129-18
Date
2016
Source
Science (New York, N.Y.)   351(6272): aad2197 (Journal)
Registered Authors
Liao, Eric, Mosimann, Christian, Santoriello, Cristina, van Rooijen, Ellen, White, Richard M., Zon, Leonard I.
Keywords
none
Datasets
GEO:GSE75355, GEO:GSE75353, GEO:GSE75351, GEO:GSE75356, GEO:GSE61823
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Carcinogenesis/genetics*
  • Embryonic Stem Cells/metabolism
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental*
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Green Fluorescent Proteins/genetics
  • Melanocytes/metabolism
  • Melanoma/genetics*
  • Melanoma, Experimental/genetics*
  • Mutation
  • Nerve Tissue Proteins/genetics
  • Neural Crest/metabolism*
  • Proto-Oncogene Proteins B-raf/genetics
  • SOXE Transcription Factors/genetics
  • Skin Neoplasms/genetics*
  • Tumor Suppressor Protein p53/genetics
  • Zebrafish*
  • Zebrafish Proteins/genetics
PubMed
26823433 Full text @ Science
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.

Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes