The Genetic Evolution of Skin Squamous Cell Carcinoma: Tumor Suppressor Identity Matters

The study explored the genetic evolution of cutaneous squamous cell carcinoma (cSCC), focusing on the role of tumor suppressor genes. It was found that mutations in the Tp53 gene were prevalent in cSCC, with frequencies ranging from 44% to 79% in advanced cases. Other genes like NOTCH1, NOTCH2, CDKN2A, and KMT2D were also frequently mutated. The research utilized mouse models to demonstrate that the deletion of specific tumor suppressor genes in hair follicle stem cells led to different tumor phenotypes. For instance, Kras activation with Tp53 deletion resulted in aggressive SCC, while Rb1 deletion led to benign papillomas. The study highlighted the importance of the identity of the tumor suppressor gene in determining tumor phenotype and suggested that future research should investigate the sequence of mutations and the role of other oncogenes and tumor suppressors in cSCC. The findings provided a foundation for developing more advanced models to identify new therapeutic targets for cSCC.