Understanding between the histone-chromatin modification and the possible augmentation of therapeutic sensitivity for malignant melanoma

BRAF （V600E）是60-70%黑色素瘤患者常见的致癌驱动突变。BRAF （V600E）突变的黑色素瘤细胞通过组蛋白-染色质修饰积累了异常基因抑制，随后这种异常与所检查的黑色素瘤细胞的转移潜力密切相关。组蛋白去乙酰化酶抑制剂（HDACi）是一种改善异常去乙酰化组蛋白的有效药物。一些HDACi能够提高去乙酰化组蛋白的水平，并使黑色素瘤细胞对治疗性细胞死亡部分敏感。不幸的是，HDACi对BRAF （V600E）阳性黑色素瘤细胞的作用并不总是足够的。因此，有必要考虑BRAF （V600E）介导的组成性激活可能维持了异常的组蛋白甲基化，并且伴随黑色素瘤发展的特定基因扩增可能参与了治疗耐药。

BRAF (V600E) is the common oncogenic driver mutation in 60-70% of melanoma patients. Melanoma cells that have BRAF (V600E) mutation accumulated aberrant gene suppression through the histone-chromatin modification, and subsequently the aberrancy was well correlated with metastatic potentials of examined melanoma cells. The histone deacetylase inhibitor (HDACi) is a potent agent to improve the aberrantly deacetylated-histones. Some of HDACi were able to improve levels of deacetylated-histones and sensitized melanoma cells to the therapeutic cell death partially. Unfortunately the effects of HDACi did not always appear sufficient for BRAF (V600E)-positive melanoma cells. Thus, it is necessary to think the possibility that BRAF (V600E)-mediated constitutive activation may maintain the abnormal histone methylation, and that particular gene amplification accompanied with melanoma development may be involved in the therapeutic resistance.