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

May 2022 in “ Cell Reports ”

Kenneth G. Trieu, Shih-Ying Tsai, Markus Eberl, Virginia Ju, Noah C. Ford, Owen J. Doane, Jamie K. Peterson, Natalia A. Veniaminova, Marina Grachtchouk, Paul W. Harms, Fredrik J. Swartling, Andrzej A. Dlugosz, Sunny Y. Wong

basal cell carcinoma BCC Ptch1 Hedgehog signaling Hh signaling Gli1 Gli2 Mycn MYCN

Studysummary In this study, researchers found that basal cell carcinomas with common Hedgehog signaling mutations may require additional mutations to hyperactivate downstream signaling and progress beyond dormancy.

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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.

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