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Nat Commun. 2016 Aug 30;7:12601. doi: 10.1038/ncomms12601.

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

Author information

1
Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
2
Department of Dermatology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
3
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
4
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
5
Northwest Diagnostic Clinic, Houston, Texas 77090, USA.
6
Skin and Laser Surgery Associates, Pasadena, Texas 77505, USA.
7
Bellaire Dermatology, Bellaire, Texas 77030, USA.
8
Sequencing and Microarray Facility, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
9
Next Generation Sequencing Facility, Smithville, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
10
Department of Dermatology, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
11
Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
12
Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02215, USA.
13
Department of Biology and Biochemistry University of Houston, Houston, Texas 77204, USA.
14
Department of Head &Neck Surgery, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
15
Department of Bioinformatics &Computational Biology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
16
Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.

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.

PMID:
27574101
PMCID:
PMC5013636
DOI:
10.1038/ncomms12601
[Indexed for MEDLINE]
Free PMC Article

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