MITF-low zebrafish melanomas reveal cells with no MITF activity at the site of 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. We performed whole bulk RNA-seq to classify zebrafish MITF-low melanoma that cluster mainly by their directionality of growth and assess their resemblance to patients’ MITF-low subgroups. Furthermore, using genetic inhibition of MITF activity we discover minimal residual disease at the site of regression and using single-cell and low input RNA-seq we characterise these MITF independent cells and show that they pre-exist in the primary tumour. We performed bulk RNAseq experiment of zebrafish primary melanomas to compare different phenotypes based on directionality of growth or original mutations. Further we performed single cell RNAseq of primary and regressed melanoma.