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

TitleCross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates.
Publication TypeJournal Article
Year of Publication2016
AuthorsChitsazzadeh, V, Coarfa, C, Drummond, JA, Nguyen, T, Joseph, A, Chilukuri, S, Charpiot, E, Adelmann, CH, Ching, G, Nguyen, TN, Nicholas, C, Thomas, VD, Migden, M, MacFarlane, D, Thompson, E, Shen, J, Takata, Y, McNiece, K, Polansky, MA, Abbas, HA, Rajapakshe, K, Gower, A, Spira, A, Covington, KR, Xiao, W, Gunaratne, P, Pickering, C, Frederick, M, Myers, JN, Shen, L, Yao, H, Su, X, Rapini, RP, Wheeler, DA, Hawk, ET, Flores, ER, Tsai, KY
JournalNat Commun
Date Published2016 Aug 30
KeywordsAnimals, Antineoplastic Agents, Carcinogenesis, Carcinoma, Squamous Cell, Disease Progression, DNA Mutational Analysis, Exome Sequencing, Female, Gene Expression Profiling, Genomics, High-Throughput Nucleotide Sequencing, Humans, Keratosis, Actinic, Mice, Mice, Hairless, Molecular Targeted Therapy, Precancerous Conditions, Sequence Analysis, RNA, Skin, Skin Neoplasms, Ultraviolet Rays

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.

Alternate JournalNat Commun
PubMed ID27574101
PubMed Central IDPMC5013636
Grant ListP30 CA016672 / CA / NCI NIH HHS / United States
R01 CA194617 / CA / NCI NIH HHS / United States
R35 CA197452 / CA / NCI NIH HHS / United States

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