Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates.
Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates.
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DOI：
10.1038/ncomms12601
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发表时间：
2016-08-30
影响因子：
16.6
通讯作者：
Tsai, Kenneth Y.
中科院分区：
文献类型：
--
作者：
Chitsazzadeh, Vida;Coarfa, Cristian;Drummond, Jennifer A.;Tri Nguyen;Joseph, Aaron;Chilukuri, Suneel;Charpiot, Elizabeth;Adelmann, Charles H.;Ching, Grace;Nguyen, Tran N.;Nicholas, Courtney;Thomas, Valencia D.;Migden, Michael;MacFarlane, Deborah;Thompson, Erika;Shen, Jianjun;Takata, Yoko;McNiece, Kayla;Polansky, Maxim A.;Abbas, Hussein A.;Rajapakshe, Kimal;Gower, Adam;Spira, Avrum;Covington, Kyle R.;Xiao, Weimin;Gunaratne, Preethi;Pickering, Curtis;Frederick, Mitchell;Myers, Jeffrey N.;Shen, Li;Yao, Hui;Su, Xiaoping;Rapini, Ronald P.;Wheeler, David A.;Hawk, Ernest T.;Flores, Elsa R.;Tsai, Kenneth Y.
皮肤鳞状细胞癌(CuSCC)占所有皮肤癌的15-20%，在美国每年约有70万例以上。大多数CuSCC与一种明显的癌前病变有关，即光化性角化病(AK)。为了确定分子靶向化学预防的潜在靶点，在这里，我们使用匹配的人类样本和太阳紫外线辐射驱动的无毛小鼠模型，通过癌前AK阶段对CuSCC的发育进行跨物种的综合基因组分析。我们确定了这一进展序列的主要转录驱动因素，表明CuSCC发育中的关键基因组变化发生在正常皮肤到AK的转变中。我们的数据验证了这种紫外线辐射驱动的小鼠CuSCC模型用于跨物种分析的有效性，并证明了CuSCC与来自不同部位的多个致癌物驱动的SCC具有深刻的分子相似性，表明CuSCC可能是一种有效的、可获得的多种SCC类型的模型，通用的治疗和预防策略可能是可行的。皮肤鳞状细胞是一种常见的肿瘤，常发生于癌前光化性角化病。在这里，作者对匹配的人类病变进行了基因组分析，并与紫外线治疗的小鼠进行了比较，确定了肿瘤发展的保守驱动因素。
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. Cutaneous squamous cell of the skin is a common neoplasm that frequently arises from precancerous actinic keratoses. Here, the authors carry out genomic analysis on matched sets of human lesions and compare with those in ultraviolet treated mice and identify conserved drivers of tumour development.
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影响因子：
4.6
作者：
Bhatia, N;Spiegelman, VS
通讯作者：
Spiegelman, VS
影响因子：
4.6
作者：
Hudson, Laurie G.;Gale, James M.;Kusewitt, Donna F.
通讯作者：
Kusewitt, Donna F.
影响因子：
30.8
作者：
Bass, Adam J.;Watanabe, Hideo;Mermel, Craig H.;Yu, Soyoung;Perner, Sven;Verhaak, Roel G.;Kim, So Young;Wardwell, Leslie;Tamayo, Pablo;Gat-Viks, Irit;Ramos, Alex H.;Woo, Michele S.;Weir, Barbara A.;Getz, Gad;Beroukhim, Rameen;O'Kelly, Michael;Dutt, Amit;Rozenblatt-Rosen, Orit;Dziunycz, Piotr;Komisarof, Justin;Chirieac, Lucian R.;LaFargue, Christopher J.;Scheble, Veit;Wilbertz, Theresia;Ma, Changqing;Rao, Shilpa;Nakagawa, Hiroshi;Stairs, Douglas B.;Lin, Lin;Giordano, Thomas J.;Wagner, Patrick;Minna, John D.;Gazdar, Adi F.;Zhu, Chang Qi;Brose, Marcia S.;Cecconello, Ivan;Ribeiro, Ulysses, Jr.;Marie, Suely K.;Dahl, Olav;Shivdasani, Ramesh A.;Tsao, Ming-Sound;Rubin, Mark A.;Wong, Kwok K.;Regev, Aviv;Hahn, William C.;Beer, David G.;Rustgi, Anil K.;Meyerson, Matthew
通讯作者：
Meyerson, Matthew
影响因子：
1.1
作者：
Eckert RL;Adhikary G;Young CA;Jans R;Crish JF;Xu W;Rorke EA
通讯作者：
Rorke EA
影响因子：
5.8
作者：
Chang, Jeffrey T.;Nevins, Joseph R.
通讯作者：
Nevins, Joseph R.