A Simple and Scalable Zebrafish Model of Sonic Hedgehog Medulloblastoma.

Medulloblastoma (MB) is the most common malignant brain tumor in children and is stratified into three major subgroups. The Sonic hedgehog (SHH) subgroup represents ~30% of all MB cases and has significant survival disparity depending upon TP53 status. Here, we describe the first zebrafish model of SHH MB using CRISPR to mutate , the primary genetic driver in human SHH MB. These tumors rapidly arise adjacent to the valvula cerebelli and resemble human SHH MB by histology and comparative genomics. In addition, -deficient MB tumors with loss of have aggressive tumor histology and significantly worse survival outcomes, comparable to human patients. The simplicity and scalability of the MB model makes it highly amenable to CRISPR-based genome editing screens to identify genes required for SHH MB tumor formation , and here we identify the kinase as one such target.