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

The study found that basal cell carcinomas (BCCs) often have a high number of mutations, but the role of these mutations was not well understood. It was observed that the loss of Ptch1, a common mutation that activates Hedgehog (Hh) signaling, led to the formation of early-stage BCC-like tumors that typically became dormant. However, some tumors overcame dormancy by acquiring secondary mutations that hyperactivated downstream Hh signaling, such as amplification of Gli1/2 and upregulation of Mycn. The research demonstrated that overexpression of MYCN facilitated the progression of tumors initiated by Ptch1 loss. This indicated that while initial mutations activating upstream Hh signaling were necessary, additional mutations were required for BCCs to progress beyond dormancy and grow uncontrollably.