Cancer-epigenetic function of the histone methyltransferase KMT2D and therapeutic opportunities for the treatment of KMT2D-deficient tumors.
Cancer-epigenetic function of the histone methyltransferase KMT2D and therapeutic opportunities for the treatment of KMT2D-deficient tumors.
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DOI：
10.18632/oncotarget.27988
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发表时间：
2021-06-22
期刊：
影响因子：
--
通讯作者：
Lee MG
中科院分区：
文献类型：
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作者：
Dhar SS;Lee MG
表观遗传学机制是理解肿瘤发生的分子基础的中心。表观遗传修饰物中的异常改变了表观基因组的格局，并在肿瘤发生中发挥了关键作用。值得注意的是，组蛋白赖氨酸甲基转移酶KMT2D(COMPASS/Set1家族成员，也称为MLL4、ALR和MLL2)是许多不同类型癌症中最常见的突变基因之一。最近的研究表明，KMT2D缺失如何在肿瘤发生过程中诱导异常的表观基因组重编程和重新连接分子通路。这些发现也对癌症治疗具有临床和治疗意义。在这篇综述中，我们总结了KMT2D在调节肿瘤发生中的作用方面的最新进展，并讨论了KMT2D缺陷肿瘤的治疗机会。
Epigenetic mechanisms are central to understanding the molecular basis underlying tumorigenesis. Aberrations in epigenetic modifiers alter epigenomic landscapes and play a critical role in tumorigenesis. Notably, the histone lysine methyltransferase KMT2D (a COMPASS/ Set1 family member; also known as MLL4, ALR, and MLL2) is among the most frequently mutated genes in many different types of cancer. Recent studies have demonstrated how KMT2D loss induces abnormal epigenomic reprograming and rewires molecular pathways during tumorigenesis. These findings also have clinical and therapeutic implications for cancer treatment. In this review, we summarize recent advances in understanding the role of KMT2D in regulating tumorigenesis and discuss therapeutic opportunities for the treatment of KMT2D-deficient tumors.