Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates
Research paper by
Vida Chitsazzadeh, Cristian Coarfa, Jennifer A. Drummond, Tri Nguyen, Aaron Joseph, Suneel Chilukuri, Elizabeth Charpiot, Charles H. Adelmann, Grace Ching, Tran N. Nguyen, Courtney Nicholas, Valencia D. Thomas, Michael Migden, Deborah MacFarlane, Erika Thompson, Jianjun Shen, Yoko Takata, Kayla McNiece, Maxim A. Polansky, Hussein A. Abbas, Kimal Rajapakshe, Adam Gower, Avrum Spira, Kyle R. Covington, Weimin Xiao, Preethi Gunaratne, Curtis Pickering, Mitchell Frederick, Jeffrey N. Myers, Li Shen, Hui Yao, Xiaoping Su, Ronald P. Rapini, David A. Wheeler, Ernest T. Hawk, Elsa R. Flores, Kenneth Y. Tsai
Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible.