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. DNA methylation: Array based methylation analysis of 59 cell lines.