DACH1基因在前列腺癌中经常被删除，抑制前列腺上皮内瘤变，减少DNA损伤修复，并预测治疗反应。
The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses.
发表日期：2023 Apr 24
作者：
Zhiping Li, Xuanmao Jiao, A Gordon Robertson, Gabriele Di Sante, Anthony W Ashton, Agnese DiRocco, Min Wang, Jun Zhao, Sankar Addya, Chenguang Wang, Peter A McCue, Andrew P South, Carlos Cordon-Cardo, Runzhi Liu, Kishan Patel, Rasha Hamid, Jorim Parmar, James B DuHadaway, Steven J M Jones, Mathew C Casimiro, Nikolaus Schultz, Andrew Kossenkov, Lai Yee Phoon, Hao Chen, Li Lan, Yunguang Sun, Kenneth A Iczkowski, Hallgeir Rui, Richard G Pestell
来源：
ONCOGENE
摘要：
前列腺癌（PCa）是美国男性死亡的第二大原因，包括具有不同基因亚型和不同治疗易感性。DACH1基因编码翅膀螺旋/叉头DNA结合蛋白，竞争性地结合FOXM1位点。在此，13q21.31-q21.33区域内DACH1基因缺失在人类前列腺癌中发生率高达18％，与增加的AR活性和恶性预后相关。在前列腺OncoMice中，特异性前列腺Dach1基因缺失增强了前列腺上皮内瘤样病变（PIN），并与增加的TGFβ活性和DNA损伤相关。缺少Dach1会增加对基因毒性应激的DNA损伤。DACH1被招募到DNA损伤位点，增强Ku70/Ku80的招募。降低的Dach1表达与增加的同源重组修复和对PARP抑制剂和TGFβ激酶抑制剂的耐药性相关。降低的Dach1表达可能定义PCa的一个亚型，需要专门的治疗。©2023年作者。
Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1 gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of the Dach1 gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFβ activity and DNA damage. Reduced Dach1 increased DNA damage in response to genotoxic stresses. DACH1 was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. Reduced Dach1 expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFβ kinase inhibitors. Reduced Dach1 expression may define a subclass of PCa that warrants specific therapies.© 2023. The Author(s).