Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

• Published in: Nature communications Vol. 7; no. 1; pp. 12601 - 17
• Main Authors: Chitsazzadeh, Vida, Coarfa, Cristian, Drummond, Jennifer A., Nguyen, Tri, Joseph, Aaron, Chilukuri, Suneel, Charpiot, Elizabeth, Adelmann, Charles H., Ching, Grace, Nguyen, Tran N., Nicholas, Courtney, Thomas, Valencia D., Migden, Michael, MacFarlane, Deborah, Thompson, Erika, Shen, Jianjun, Takata, Yoko, McNiece, Kayla, Polansky, Maxim A., Abbas, Hussein A., Rajapakshe, Kimal, Gower, Adam, Spira, Avrum, Covington, Kyle R., Xiao, Weimin, Gunaratne, Preethi, Pickering, Curtis, Frederick, Mitchell, Myers, Jeffrey N., Shen, Li, Yao, Hui, Su, Xiaoping, Rapini, Ronald P., Wheeler, David A., Hawk, Ernest T., Flores, Elsa R., Tsai, Kenneth Y.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 38/39; 631/67/1813/1352; 631/67/69; 64; 64/60; Animals; Antineoplastic Agents - therapeutic use; Biochemistry; Biology; Cancer therapies; Carcinogenesis - genetics; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - prevention & control; Dermatology; Disease prevention; Disease Progression; DNA Mutational Analysis; Female; Gene Expression Profiling; Genomes; Genomics; High-Throughput Nucleotide Sequencing; Humanities and Social Sciences; Humans; Keratosis, Actinic - pathology; Medicine; Mice; Mice, Hairless; Molecular Targeted Therapy - methods; multidisciplinary; Precancerous Conditions - genetics; Precancerous Conditions - pathology; Science; Science (multidisciplinary); Sequence Analysis, RNA; Skin - pathology; Skin Neoplasms - etiology; Skin Neoplasms - genetics; Skin Neoplasms - prevention & control; Solar radiation; Surgery; Ultraviolet radiation; Ultraviolet Rays - adverse effects; Whole Exome Sequencing; United States > US; Texas
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12601

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. Cutaneous squamous cell of the skin is a common neoplasm that frequently arises from precancerous actinic keratoses. Here, the authors carry out genomic analysis on matched sets of human lesions and compare with those in ultraviolet treated mice and identify conserved drivers of tumour development.