Okawa Ryuichiro, Banno Kouji, Iida Miho, Yanokura Megumi, Takeda Takashi, Iijima Moito, Kunitomi-Irie Haruko, Nakamura Kanako, Adachi Masataka, Umene Kiyoko, Nogami Yuya, Masuda Kenta, Kobayashi Yusuke, Tominaga Eiichiro, Aoki Daisuke
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Oncol Lett. 2017 Nov;14(5):5107-5113. doi: 10.3892/ol.2017.6891. Epub 2017 Sep 6.
Epigenetic regulatory mechanisms are a current focus in studies investigating cancer. Chromatin remodeling alters chromatin structure and regulates gene expression, and aberrant chromatin remodeling is involved in carcinogenesis. AT-rich interactive domain-containing protein 1A (ARID1A) and SWItch/sucrose non-fermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 are remodeling factors that are mutated in numerous types of cancer. In gynecological cancer, mutations have been identified in 46-57% of clear cell carcinoma and 30% of endometrioid carcinoma. Mutations of chromodomain helicase, DNA-binding protein 4 have been detected in 17-21% of endometrial serous cancer, and mutations of and mixed-lineage leukemia 3 occur in 36 and 27% of uterine carcinosarcoma, respectively. These data suggest that aberrant chromatin remodeling is a potential cause of cancer, and have led to the development of novel proteins targeting these processes. Additional accumulation of information on the mechanisms of chromatin remodeling and markers for these events may promote personalized anticancer therapies.
表观遗传调控机制是当前癌症研究的重点。染色质重塑改变染色质结构并调节基因表达,异常的染色质重塑参与致癌过程。富含AT的互作结构域蛋白1A(ARID1A)和与SWItch/蔗糖非发酵相关、基质相关、肌动蛋白依赖性染色质调节因子a亚家族成员4是在多种癌症中发生突变的重塑因子。在妇科癌症中,46%-57%的透明细胞癌和30%的子宫内膜样癌中已发现突变。在17%-21%的子宫内膜浆液性癌中检测到染色质结构域解旋酶DNA结合蛋白4的突变,混合谱系白血病3的突变分别发生在36%和27%的子宫癌肉瘤中。这些数据表明,异常的染色质重塑是癌症的潜在原因,并导致了针对这些过程的新型蛋白质的开发。关于染色质重塑机制和这些事件标志物的更多信息积累可能会促进个性化抗癌治疗。