Laugesen Anne, Højfeldt Jonas Westergaard, Helin Kristian
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen N, Denmark Centre for Epigenetics, University of Copenhagen, DK-2200 Copenhagen N, Denmark The Danish Stem Cell Center (DanStem), University of Copenhagen, DK-2200 Copenhagen N, Denmark.
Cold Spring Harb Perspect Med. 2016 Sep 1;6(9):a026575. doi: 10.1101/cshperspect.a026575.
The chromatin environment is modulated by a machinery of chromatin modifiers, required for the specification and maintenance of cell fate. Many mutations in the machinery have been linked to the development and progression of cancer. In this review, we give a brief introduction to Polycomb group (PcG) proteins, their assembly into Polycomb repressive complexes (PRCs) and the normal physiological roles of these complexes with a focus on the PRC2. We review the many findings of mutations in the PRC2 coding genes, both loss-of-function and gain-of-function, associated with human cancers and discuss potential molecular mechanisms involved in the contribution of PRC2 mutations to cancer development and progression. Finally, we discuss some of the recent advances in developing and testing drugs targeting the PRC2 as well as emerging results from clinical trials using these drugs in the treatment of human cancers.
染色质环境由染色质修饰因子机制调控，这对于细胞命运的决定和维持至关重要。该机制中的许多突变都与癌症的发生和发展有关。在本综述中，我们简要介绍了多梳蛋白家族（PcG）蛋白、它们组装成多梳抑制复合物（PRCs）以及这些复合物的正常生理作用，重点是PRC2。我们回顾了与人类癌症相关的PRC2编码基因的许多突变发现，包括功能丧失和功能获得突变，并讨论了PRC2突变对癌症发生和发展的潜在分子机制。最后，我们讨论了开发和测试靶向PRC2药物的一些最新进展，以及使用这些药物治疗人类癌症的临床试验的新结果。
