title: 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.
authors: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.|Department of Dermatology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Vida
authors: V
authors: Chitsazzadeh
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Cristian
authors: C
authors: Coarfa
authors: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Jennifer A
authors: JA
authors: Drummond
authors: Northwest Diagnostic Clinic, Houston, Texas 77090, USA.
authors: Tri
authors: T
authors: Nguyen
authors: Skin and Laser Surgery Associates, Pasadena, Texas 77505, USA.
authors: Aaron
authors: A
authors: Joseph
authors: Bellaire Dermatology, Bellaire, Texas 77030, USA.
authors: Suneel
authors: S
authors: Chilukuri
authors: Bellaire Dermatology, Bellaire, Texas 77030, USA.
authors: Elizabeth
authors: E
authors: Charpiot
authors: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.|Department of Dermatology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Charles H
authors: CH
authors: Adelmann
authors: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.|Department of Dermatology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Grace
authors: G
authors: Ching
authors: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Tran N
authors: TN
authors: Nguyen
authors: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Courtney
authors: C
authors: Nicholas
authors: Department of Dermatology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Valencia D
authors: VD
authors: Thomas
authors: Department of Dermatology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Michael
authors: M
authors: Migden
authors: Department of Dermatology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Deborah
authors: D
authors: MacFarlane
authors: Sequencing and Microarray Facility, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Erika
authors: E
authors: Thompson
authors: Next Generation Sequencing Facility, Smithville, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Jianjun
authors: J
authors: Shen
authors: Next Generation Sequencing Facility, Smithville, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Yoko
authors: Y
authors: Takata
authors: Department of Dermatology, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
authors: Kayla
authors: K
authors: McNiece
authors: Department of Dermatology, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
authors: Maxim A
authors: MA
authors: Polansky
authors: Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Hussein A
authors: HA
authors: Abbas
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Kimal
authors: K
authors: Rajapakshe
authors: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02215, USA.
authors: Adam
authors: A
authors: Gower
authors: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02215, USA.
authors: Avrum
authors: A
authors: Spira
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Kyle R
authors: KR
authors: Covington
authors: Department of Biology and Biochemistry University of Houston, Houston, Texas 77204, USA.
authors: Weimin
authors: W
authors: Xiao
authors: Department of Biology and Biochemistry University of Houston, Houston, Texas 77204, USA.
authors: Preethi
authors: P
authors: Gunaratne
authors: Department of Head &Neck Surgery, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Curtis
authors: C
authors: Pickering
authors: Department of Head &Neck Surgery, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Mitchell
authors: M
authors: Frederick
authors: Department of Head &Neck Surgery, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Jeffrey N
authors: JN
authors: Myers
authors: Department of Bioinformatics &Computational Biology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Li
authors: L
authors: Shen
authors: Department of Bioinformatics &Computational Biology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Hui
authors: H
authors: Yao
authors: Department of Bioinformatics &Computational Biology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Xiaoping
authors: X
authors: Su
authors: Department of Dermatology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.|Department of Dermatology, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
authors: Ronald P
authors: RP
authors: Rapini
authors: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: David A
authors: DA
authors: Wheeler
authors: Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Ernest T
authors: ET
authors: Hawk
authors: Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Elsa R
authors: ER
authors: Flores
authors: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.|Department of Dermatology, University of Texas MD Anderson Cancer Center Houston, Houston, Texas 77030, USA.
authors: Kenneth Y
authors: KY
authors: Tsai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D063646:Carcinogenesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D055623:Keratosis, Actinic / Q000473:pathology*; D051379:Mice; D008812:Mice, Hairless; D058990:Molecular Targeted Therapy / Q000379:methods; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D017423:Sequence Analysis, RNA; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D014466:Ultraviolet Rays / Q000009:adverse effects; D000073359:Exome Sequencing
chemical_list: D000970:Antineoplastic Agents