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

被引：117

作者：

Chitsazzadeh, Vida ^{[1
,2
]}

Coarfa, Cristian ^{[3
]}

Drummond, Jennifer A. ^{[4
]}

Tri Nguyen ^{[5
]}

Joseph, Aaron ^{[6
]}

Chilukuri, Suneel ^{[7
]}

Charpiot, Elizabeth ^{[7
]}

Adelmann, Charles H. ^{[1
,2
]}

Ching, Grace ^{[1
,2
]}

Nguyen, Tran N. ^{[1
]}

Nicholas, Courtney ^{[1
]}

Thomas, Valencia D. ^{[2
]}

Migden, Michael ^{[2
]}

MacFarlane, Deborah ^{[2
]}

Thompson, Erika ^{[8
]}

Shen, Jianjun ^{[9
]}

Takata, Yoko ^{[9
]}

McNiece, Kayla ^{[10
]}

Polansky, Maxim A. ^{[10
]}

Abbas, Hussein A. ^{[11
]}

Rajapakshe, Kimal ^{[3
]}

Gower, Adam ^{[12
]}

Spira, Avrum ^{[12
]}

Covington, Kyle R. ^{[3
,4
]}

Xiao, Weimin ^{[13
]}

Gunaratne, Preethi ^{[13
]}

Pickering, Curtis ^{[14
]}

Frederick, Mitchell ^{[14
]}

Myers, Jeffrey N. ^{[14
]}

Shen, Li ^{[15
]}

Yao, Hui ^{[15
]}

Su, Xiaoping ^{[15
]}

Rapini, Ronald P. ^{[2
,10
]}

Wheeler, David A. ^{[3
,4
]}

Hawk, Ernest T. ^{[16
]}

Flores, Elsa R. ^{[11
]}

Tsai, Kenneth Y. ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, 1515 Holcombe Blvd, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[4] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[5] Northwest Diagnost Clin, Houston, TX 77090 USA

[6] Skin & Laser Surg Associates, Pasadena, TX 77505 USA

[7] Bellaire Dermatol, Bellaire, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Sequencing & Microarray Facil, Houston, TX 77030 USA

[9] Univ Texas MD Anderson Canc Ctr, Next Generat Sequencing Facil, Houston, TX 77030 USA

[10] Univ Texas Houston, Sch Med, Dept Dermatol, Houston, TX 77030 USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[12] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA

[13] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA

[14] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA

[15] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[16] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

关键词：

GENE NUMERICAL ABERRATIONS; ACTINIC KERATOSIS; RAS MUTATIONS; CHROMOSOMAL-ABERRATIONS; BARRETTS-ESOPHAGUS; HUMAN SKIN; EXPRESSION; MOUSE; LUNG; LANDSCAPE;

D O I：

10.1038/ncomms12601

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：17

共 81 条

[81] MUTATION HOTSPOTS DUE TO SUNLIGHT IN THE P53 GENE OF NONMELANOMA SKIN CANCERS [J].

ZIEGLER, A ;

LEFFELL, DJ ;

KUNALA, S ;

SHARMA, HW ;

GAILANI, M ;

SIMON, JA ;

HALPERIN, AJ ;

BADEN, HP ;

SHAPIRO, PE ;

BALE, AE ;

BRASH, DE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (09) :4216-4220

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