|ZFIN ID: ZDB-PUB-180609-27|
Neural crest state activation in NRAS driven melanoma, but not in NRAS-driven melanocyte expansion
McConnell, A.M., Mito, J.K., Ablain, J., Dang, M., Formichella, L., Fisher, D.E., Zon, L.I.
|Source:||Developmental Biology 449(2): 107-114 (Journal)|
|Registered Authors:||Zon, Leonard I.|
|Keywords:||NRAS, Neural crest, cancer, melanoma|
|PubMed:||29883661 Full text @ Dev. Biol.|
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.
ABSTRACTNRAS 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.