Basal Cell Carcinomas Acquire Secondary Mutations to Overcome Dormancy and Progress from Microscopic to Macroscopic Disease

The study investigated the progression of basal cell carcinomas (BCCs) from dormancy to macroscopic disease, emphasizing the role of secondary mutations. Initial tumor formation was triggered by Ptch1 loss, activating Hedgehog (Hh) signaling, but further progression required additional mutations, such as Gli1/2 amplification and Mycn upregulation. These secondary mutations were crucial for overcoming dormancy and driving tumor growth. The study used whole-exome sequencing on 21 mouse BCC-like tumors and found that macroscopic tumors exhibited high proliferation, reduced Notch signaling, and elevated MYCN levels. The research highlighted the complexity of BCC progression and suggested that targeting these pathways could be important for treatment, although differences between mouse models and human BCCs were noted.