MITF-low melanoma subtype models in zebrafish reveal transcriptional sub-clusters and MITF-independent residual disease

The MITF-low melanoma transcriptional signature is predictive of poor outcome for patients but little is known about its biological signature. We used genetic models of zebrafish with low expression of mitfa (MITF-low) to study this biological subtype. Using genetic inhibition of MITF activity we discover minimal residual disease at the site of regression. We performed single cell RNA-seq (Smart-seq2) to characterise cells at the site of residual disease, and put in relation with primary tumours and recurring disease. We performed single cell RNAseq experiment (Smart-seq2) of zebrafish primary superficial and nodular melanomas, corresponding residual diseases and beginning of recurrence (nodular melanoma only).