Loss of Kdm6a and Trp53 drives the development of squamous cell skin cancer in mice

Cutaneous squamous cell carcinoma (cSCC) has among the highest mutation burdens of all cancers, reflecting its association with the mutagenic effects of ultraviolet light. Though mutations in established, cancer-relevant genes like TP53 and NOTCH1 are prevalent in cSCC, they are tolerated in clinically normal skin and are insufficient to cause skin cancer. Whether epigenetic regulators cooperate in the development of squamous cell carcinoma is just starting to be defined. KDM6A encodes a histone H3K27me2/me3 demethylase that is frequently mutated in cSCC and other cancers.