2021/09/03
论文
论文标题：Developmental chromatin programs determine oncogenic competence in melanoma
作者：Arianna Baggiolini, Scott J. Callahan, Tuan Trieu, Mohita M. Tagore, Emily Montal, Joshua M. Weiss, Sam E. Tischfield, Yujie Fan, Nathaniel R. Campbell, Nathalie Saurat, Travis Hollmann, Theresa Simon-Vermot, Satish K. Tickoo, Barry S. Taylor, Richard Koche, Ekta Khurana, Lorenz Studer, Richard M. White
期刊：bioRxiv
发表时间：2020/05/10
数字识别码：10.1101/2020.05.09.081554
摘要：Oncogenes are only transforming in certain cellular contexts, a phenomenon called oncogenic competence. The mechanisms regulating this competence remain poorly understood. Here, using a combination of a novel human pluripotent stem cell (hPSC)-based cancer model along with zebrafish transgenesis, we demonstrate that the transforming ability of BRAFV600E depends upon the intrinsic transcriptional program present in the cell of origin. Remarkably, in both systems, melanocytes (MC) are largely resistant to BRAF. In contrast, both neural crest (NC) and melanoblast (MB) populations are readily transformed. Molecular profiling reveals that NC/MB cells have markedly higher expression of chromatin modifying enzymes, and we discovered that the chromatin remodeler ATAD2 is required for response to BRAF and tumor initiation. ATAD2 forms a complex with SOX10, allowing for expression of downstream oncogenic programs. These data suggest that oncogenic competence is mediated by developmental regulation of chromatin factors, which then allow for proper response to those oncogenes.
