Murine Kdm6a and Trp53 null squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) has among the highest mutation burdens of all cancers, reflecting its pathogenic association with the mutagenic effects of ultraviolet light exposure. Although mutations in cancer-relevant genes like TP53 and NOTCH1 are common in cSCC, they are also tolerated in normal skin and suggest that other events are required for transformation; it is not yet clear whether epigenetic regulators cooperate in the pathogenesis of cSCC. KDM6A encodes a histone H3K27me2/me3 demethylase that is frequently mutated in cSCC and other cancers. We generated mice with epidermal deficiency of both Kdm6a and Trp53 which exhibited 100% penetrant, spontaneous cSCC development within a year and performed exome sequencing of resulting tumors.