Melanoma is an aggressive, deadly skin cancer derived from melanocytes, a neural crest cell derivative. Melanoma cells mirror the developmental program of neural crest cells in that they exhibit the same gene expression patterns and utilize similar cellular mechanisms, including increased cell proliferation, epithelial‐mesenchymal transition, and migration. Here we studied the role of neural crest regulator PRDM1 in melanoma onset and progression. In development, Prdm1a functions to promote neural crest progenitor fate, and in melanoma, we found that PRDM1 has reduced copy number and is recurrently deleted in both zebrafish and humans. When examining expression of neural crest and melanocyte development genes, we show that sox10 progenitor expression is high in prdm1a^−/− mutants, while more differentiated melanocyte markers are reduced, suggesting that normally Prdm1a is required for differentiation. Data mining of human melanoma datasets indicates that high PRDM1 expression in human melanoma is correlated with better patient survival and decreased PRDM1 expression is common in metastatic tumors. When one copy of prdm1a is lost in the zebrafish melanoma model Tg(mitfa:BRAF^V600E);p53 ^−/−;prdm1a ^+/−, melanoma onset occurs more quickly, and the tumors that form have a larger area with increased expression of sox10 . These data demonstrate a novel role for PRDM1 as a tumor suppressor in melanoma.

中文翻译：

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prdm1a 的缺失会加速黑色素瘤的发生和进展。

黑色素瘤是一种侵袭性、致命的皮肤癌，源自黑色素细胞，黑色素细胞是一种神经嵴细胞衍生物。黑色素瘤细胞反映了神经嵴细胞的发育程序，因为它们表现出相同的基因表达模式并利用相似的细胞机制，包括增加细胞增殖、上皮间质转化和迁移。在这里，我们研究了神经嵴调节器 PRDM1 在黑色素瘤发病和进展中的作用。在开发过程中，Prdm1a 的功能是促进神经嵴祖细胞的命运，在黑色素瘤中，我们发现PRDM1 的拷贝数减少，并且在斑马鱼和人类中反复被删除。当检查神经嵴和黑色素细胞发育的基因的表达，我们表明，SOX10祖表达是高prdm1a^-/- 突变体，而更多分化的黑素细胞标记物减少，表明通常需要 Prdm1a 进行分化。人类黑色素瘤数据集的数据挖掘表明，人类黑色素瘤中PRDM1 的高表达与更好的患者生存相关，而PRDM1表达降低在转移性肿瘤中很常见。当在斑马鱼黑色素瘤模型 Tg(mitfa:BRAF ^V600E ) 中丢失一份prdm1a 时；p53 ^-/- ; prdm1a ^+/-，黑色素瘤发病更快，形成的肿瘤面积更大， sox10表达增加. 这些数据证明了 PRDM1 作为黑色素瘤中的肿瘤抑制因子的新作用。