Because we previously showed that UF driver mutations in MED12 disrupt CDK8/19 kinase function [13, 16, 28], we profiled the transcriptome of CDK8/19-inhibited MM SCs and found that Mediator kinase inhibition triggered spontaneous myogenesis down an altered pathway characterized by molecular phenotypes characteristic of UFs, including oncogenic growth and extracellular matrix (ECM) production. Here, MED12 is linked to Miyoshi myopathy.