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 highlighted that mutations in genes like Tp53, NOTCH1, and NOTCH2 are common in cSCC, with Tp53 mutations occurring in 44% to 79% of cases. The research used mouse models to demonstrate that the deletion of specific tumor suppressor genes in hair follicle stem cells leads to different tumor phenotypes. For instance, Kras activation with Tp53 deletion resulted in aggressive squamous cell carcinoma, while Kras activation with Rb1 or Pten deletion led to benign tumors. This indicated that the identity of the tumor suppressor gene lost influences the tumor's phenotype. The study suggested that future research should investigate the roles of other frequently mutated genes in cSCC and the sequence of mutations, using advanced technologies like CRISPR/CAS9 for more comprehensive models.