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


ABSTRACT: 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.

SUBMITTER: Chitsazzadeh V 

PROVIDER: S-EPMC5013636 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Chitsazzadeh Vida V   Coarfa Cristian C   Drummond Jennifer A JA   Nguyen Tri T   Joseph Aaron A   Chilukuri Suneel S   Charpiot Elizabeth E   Adelmann Charles H CH   Ching Grace G   Nguyen Tran N TN   Nicholas Courtney C   Thomas Valencia D VD   Migden Michael M   MacFarlane Deborah D   Thompson Erika E   Shen Jianjun J   Takata Yoko Y   McNiece Kayla K   Polansky Maxim A MA   Abbas Hussein A HA   Rajapakshe Kimal K   Gower Adam A   Spira Avrum A   Covington Kyle R KR   Xiao Weimin W   Gunaratne Preethi P   Pickering Curtis C   Frederick Mitchell M   Myers Jeffrey N JN   Shen Li L   Yao Hui H   Su Xiaoping X   Rapini Ronald P RP   Wheeler David A DA   Hawk Ernest T ET   Flores Elsa R ER   Tsai Kenneth Y KY  

Nature communications 20160830


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 mo  ...[more]

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