PUBLICATION
Neural crest state activation in NRAS driven melanoma, but not in NRAS-driven melanocyte expansion
- Authors
- McConnell, A.M., Mito, J.K., Ablain, J., Dang, M., Formichella, L., Fisher, D.E., Zon, L.I.
- ID
- ZDB-PUB-180609-27
- Date
- 2018
- Source
- Developmental Biology 449(2): 107-114 (Journal)
- Registered Authors
- Zon, Leonard I.
- Keywords
- NRAS, Neural crest, cancer, melanoma
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Proliferation/genetics*
- Disease Models, Animal
- GTP Phosphohydrolases/genetics
- GTP Phosphohydrolases/metabolism
- Genes, ras/genetics*
- Humans
- Kaplan-Meier Estimate
- Melanocytes/metabolism*
- Melanocytes/pathology
- Melanoma/genetics*
- Melanoma/metabolism
- Melanoma/pathology
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Mutation*
- Neural Crest/metabolism*
- Skin Neoplasms/genetics*
- Skin Neoplasms/metabolism
- Skin Neoplasms/pathology
- Time Factors
- Zebrafish
- PubMed
- 29883661 Full text @ Dev. Biol.
Citation
McConnell, A.M., Mito, J.K., Ablain, J., Dang, M., Formichella, L., Fisher, D.E., Zon, L.I. (2018) Neural crest state activation in NRAS driven melanoma, but not in NRAS-driven melanocyte expansion. Developmental Biology. 449(2):107-114.
Abstract
NRAS mutations are frequently found in many deadly malignancies and are the second most common oncogene driving malignant melanoma. Here, we generate a rapid transient transgenic zebrafish model of NRASQ61R-mutant melanoma. These fish develop extensive melanocytic proliferation in approximately 4 weeks. The majority of these lesions do not engraft upon transplantation and lack overt histologic features of malignancy. Our previous work demonstrated that activation of a neural crest cell transcriptional program is a key initiating event in zebrafish BRAF/p53-driven melanomas using the fluorescent reporter crestin:EGFP. By 8-12 weeks of age, some lesions progress to malignant melanoma and have cytologic atypia, destructive tissue invasion, and express neural crest progenitor markers, including crestin:EGFP. Our studies demonstrate that NRASQ61R induces extensive melanocyte expansion, which arise during zebrafish development and lack a transformed phenotype. These early lesions are highly predisposed to reactivate a neural crest progenitor fate and form malignant melanomas.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping