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

Vida Chitsazzadeh; Cristian Coarfa; Jennifer A. Drummond; Tri Nguyen; Aaron Joseph; Suneel Chilukuri; Elizabeth Charpiot; Charles H. Adelmann; Grace Ching; Tran N. Nguyen; Courtney Nicholas; Valencia D. Thomas; Michael Migden; Deborah MacFarlane; Erika Thompson; Jianjun Shen; Yoko Takata; Kayla McNiece; Maxim A. Polansky; Hussein A. Abbas; Kimal Rajapakshe; Adam Gower; Avrum Spira; Kyle R. Covington; Weimin Xiao; Preethi Gunaratne; Curtis Pickering; Mitchell Frederick; Jeffrey N. Myers; Li Shen; Hui Yao; Xiaoping Su; Ronald P. Rapini; David A. Wheeler; Ernest T. Hawk; Elsa R. Flores; Kenneth Y. Tsai

doi:10.1038/ncomms12601

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

Vida Chitsazzadeh, Cristian Coarfa, Jennifer A. Drummond, Tri Nguyen, Aaron Joseph, Suneel Chilukuri, Elizabeth Charpiot, Charles H. Adelmann, Grace Ching, Tran N. Nguyen, Courtney Nicholas, Valencia D. Thomas, Michael Migden, Deborah MacFarlane, Erika Thompson, Jianjun Shen, Yoko Takata, Kayla McNiece, Maxim A. Polansky, Hussein A. AbbasKimal Rajapakshe, Adam Gower, Avrum Spira, Kyle R. Covington, Weimin Xiao, Preethi Gunaratne, Curtis Pickering, Mitchell Frederick, Jeffrey N. Myers, Li Shen, Hui Yao, Xiaoping Su, Ronald P. Rapini, David A. Wheeler, Ernest T. Hawk, Elsa R. Flores, Kenneth Y. Tsai

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120 Scopus citations

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.

Original language	English (US)
Article number	12601
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12601
State	Published - Aug 30 2016

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

MD Anderson CCSG core facilities

Advanced Technology Genomics Core
Bioinformatics Shared Resource
Research Animal Support Facility
Tissue Biospecimen and Pathology Resource
Clinical Trials Office

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10.1038/ncomms12601

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Chitsazzadeh, V., Coarfa, C., Drummond, J. A., Nguyen, T., Joseph, A., Chilukuri, S., Charpiot, E., Adelmann, C. H., Ching, G., Nguyen, T. N., Nicholas, C., Thomas, V. D., Migden, M., MacFarlane, D., Thompson, E., Shen, J., Takata, Y., McNiece, K., Polansky, M. A., ... Tsai, K. Y. (2016). Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates. Nature communications, 7, Article 12601. https://doi.org/10.1038/ncomms12601

Chitsazzadeh, 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 2016, 'Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates', Nature communications, vol. 7, 12601. https://doi.org/10.1038/ncomms12601

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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.",

author = "Vida Chitsazzadeh and Cristian Coarfa and Drummond, {Jennifer A.} and Tri Nguyen and Aaron Joseph and Suneel Chilukuri and Elizabeth Charpiot and Adelmann, {Charles H.} and Grace Ching and Nguyen, {Tran N.} and Courtney Nicholas and Thomas, {Valencia D.} and Michael Migden and Deborah MacFarlane and Erika Thompson and Jianjun Shen and Yoko Takata and Kayla McNiece and Polansky, {Maxim A.} and Abbas, {Hussein A.} and Kimal Rajapakshe and Adam Gower and Avrum Spira and Covington, {Kyle R.} and Weimin Xiao and Preethi Gunaratne and Curtis Pickering and Mitchell Frederick and Myers, {Jeffrey N.} and Li Shen and Hui Yao and Xiaoping Su and Rapini, {Ronald P.} and Wheeler, {David A.} and Hawk, {Ernest T.} and Flores, {Elsa R.} and Tsai, {Kenneth Y.}",

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year = "2016",

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doi = "10.1038/ncomms12601",

language = "English (US)",

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AU - Chitsazzadeh, Vida

AU - Coarfa, Cristian

AU - Drummond, Jennifer A.

AU - Nguyen, Tri

AU - Joseph, Aaron

AU - Chilukuri, Suneel

AU - Charpiot, Elizabeth

AU - Adelmann, Charles H.

AU - Ching, Grace

AU - Nguyen, Tran N.

AU - Nicholas, Courtney

AU - Thomas, Valencia D.

AU - Migden, Michael

AU - MacFarlane, Deborah

AU - Thompson, Erika

AU - Shen, Jianjun

AU - Takata, Yoko

AU - McNiece, Kayla

AU - Polansky, Maxim A.

AU - Abbas, Hussein A.

AU - Rajapakshe, Kimal

AU - Gower, Adam

AU - Spira, Avrum

AU - Covington, Kyle R.

AU - Xiao, Weimin

AU - Gunaratne, Preethi

AU - Pickering, Curtis

AU - Frederick, Mitchell

AU - Myers, Jeffrey N.

AU - Shen, Li

AU - Yao, Hui

AU - Su, Xiaoping

AU - Rapini, Ronald P.

AU - Wheeler, David A.

AU - Hawk, Ernest T.

AU - Flores, Elsa R.

AU - Tsai, Kenneth Y.

PY - 2016/8/30

Y1 - 2016/8/30

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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