TRPS1 is a lineage-specific transcriptional dependency in breast cancer [methylation array]. TRPS1 is a lineage-specific transcriptional dependency in breast cancer [methylation array]

We performed an unbiased cell viability-based pooled shRNA screen on 59 cell lines to identify novel epigenetic and transcriptional dependencies of multiple cancer types, including leukemia, neuroblastoma, breast, colorectal, prostate, and rhabdoid tumors. Here, we identified Tricho-Rhino-Phalangeal Syndrome Type I protein (TRPS1) as one of the most significant hits specific for breast cancer cell lines. Downregulation of TRPS1 resulted in cell cycle arrest and apoptosis increase in vitro and impaired tumorigenic capacity in vivo. We characterized TRPS1 genomic targets and protein interactome. We identified GATAD2B as an important partner of TRPS1, uncovering novel epigenetic network crucial for breast cancer cell survival. Overall design: DNA methylation: Array based methylation analysis of 59 cell lines.

本研究针对59株细胞系开展基于细胞活力的无偏混合shRNA筛选，旨在鉴定白血病、神经母细胞瘤、乳腺癌、结直肠癌、前列腺癌及横纹肌样瘤等多种癌症类型中新的表观遗传与转录依赖特征。
本研究在此筛选中鉴定出毛发-鼻-指（趾）综合征I型蛋白（Tricho-Rhino-Phalangeal Syndrome Type I protein，TRPS1）是乳腺癌细胞系特异性的最显著阳性靶点之一。
体外实验显示，下调TRPS1可引发细胞周期阻滞与细胞凋亡水平升高，并在体内削弱肿瘤发生能力。
本研究对TRPS1的基因组靶点与蛋白质相互作用组进行了系统表征。
本研究同时鉴定出GATAD2B是TRPS1的重要互作伴侣，由此揭示了对乳腺癌细胞存活至关重要的新型表观遗传调控网络。
整体实验设计：DNA甲基化分析：针对59株细胞系开展的基于芯片的甲基化检测。