Loss of prdm1a accelerates melanoma onset and progression

Melanoma is an aggressive and deadly skin cancer that develops from melanocytes, a neural crest cell derivative. Melanoma cells and neural crest cells share similar gene expression, behaviors, and cellular mechanisms. Using cross-species oncogenomics, we identified genes recurrently deleted in both human and zebrafish melanomas, which includes PRDM1/prdm1a, a neural crest developmental regulator. We investigated its role in melanoma tumor formation using datasets, human tissue arrays, and transgenic zebrafish lines. High PRDM1 expression in melanoma patients is correlated with better patient survival. We used a stable transgenic zebrafish line, Tg(mitfa:BRAFV600E);p53-/-, and found that when one copy of prdm1a was mutated, melanoma onset occurred more quickly and the resulting tumors were more invasive. We then analyzed expression of a downstream target and well-established melanoma marker, SOX10, and found in the human and zebrafish data, when PRDM1 expression is low, SOX10 is correspondingly high. Thus, the mechanism by which PRDM1 functions as a tumor suppressor in melanoma is likely through regulation of SOX10 expression.