Ford David J, Dingwall Andrew K
Molecular Biology and Biochemistry Graduate Program, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.
Molecular Biology and Biochemistry Graduate Program, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA; Oncology Research Institute and Department of Pathology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.
Cancer Genet. 2015 May;208(5):178-91. doi: 10.1016/j.cancergen.2015.01.005. Epub 2015 Jan 30.
The mixed-lineage leukemia family of histone methyltransferases (MLL1-4, or KMT2A-D) were previously linked to cancer through the founding member, MLL1/KMT2A, which is often involved in translocation-associated gene fusion events in childhood leukemias. However, in recent years, a multitude of tumor exome sequencing studies have revealed that orthologues MLL3/KMT2C and MLL2/KMT2D are mutated in a significant percentage of a large variety of malignancies, particularly solid tumors. These unexpected findings necessitate a deeper inspection into the activities and functional differences between the MLL/KMT2 family members. This review provides an overview of this protein family and its relation to cancers, focusing on the recent links between MLL3/KMT2C and MLL2/4/KMT2D and their potential roles as tumor suppressors in an assortment of cell types.
组蛋白甲基转移酶的混合谱系白血病家族（MLL1 - 4，即KMT2A - D）先前是通过其创始成员MLL1/KMT2A与癌症联系起来的，MLL1/KMT2A常参与儿童白血病中与易位相关的基因融合事件。然而，近年来，大量肿瘤外显子测序研究表明，直系同源基因MLL3/KMT2C和MLL2/KMT2D在多种恶性肿瘤（特别是实体瘤）中存在显著比例的突变。这些意外发现需要对MLL/KMT2家族成员之间的活性和功能差异进行更深入的研究。本综述概述了这个蛋白质家族及其与癌症的关系，重点关注MLL3/KMT2C和MLL2/4/KMT2D之间的最新联系以及它们在多种细胞类型中作为肿瘤抑制因子的潜在作用。
