Molecular characterization and integrative genomic analysis of a panel of newly established penile cancer cell lines.
Molecular characterization and integrative genomic analysis of a panel of newly established penile cancer cell lines.
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一组新建立的阴茎癌细胞的分子特征和综合基因组分析
DOI：
10.1038/s41419-018-0736-1
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发表时间：
2018-06-07
影响因子：
9
通讯作者：
Liu RY
中科院分区：
文献类型：
--
作者：
Zhou QH;Deng CZ;Li ZS;Chen JP;Yao K;Huang KB;Liu TY;Liu ZW;Qin ZK;Zhou FJ;Huang W;Han H;Liu RY
细胞系模型是研究肿瘤发生和发展的分子机制的重要工具。阴茎鳞状细胞癌（PSCC）的治疗选择有限，占发展中国家男性肿瘤的1-2%，由于缺乏具有确定基因组特征的可用模型，PSCC的临床前研究进展有限。在这里，生物学和分子特征和全基因组的改变进行了分析，在我们实验室新建立的一组PSCC细胞系。这些细胞系均为人乳头瘤病毒（HPV）阴性、上皮样、永生化和裸鼠致瘤性，但它们在体外表现出不同的增殖、迁移和侵袭能力，以及在裸鼠体内的致瘤能力。他们都是顺铂敏感，抗EGFR治疗耐药，雄激素无反应。全基因组测序分析显示，转换突变（C：G>T：A和T：A>C：G）是这些细胞系中最常见的替换类型，而ERCC 5、TP 53、PTH 1、CLTCL 1、NOTCH 2、MAP 2K 3、CDK 11 A/B、USP 6、ADCH 5、BCLAF 1、CDKN 2A、FANCD 2、HRAS和NOTCH 1是最常见的改变基因。在细胞系中经常观察到MYC、PLAG 1、NCOA 2、RUNX 1 T1、COX 6C和EGFR的扩增以及FBXW 7、TET 2、XPC和FANCE的丢失。细胞系与其对应的癌组织之间的外显子组变异高度一致。遗传变异主要涉及MAPK、Jak-STAT、TGF-β、Notch和凋亡信号通路。结论：本实验室建立的PSCC细胞系具有一些共同或特异的生物学特性和基因组变异，可作为研究PSCC进展、转移、复发和耐药的分子机制以及制定有效治疗策略的理想模型。
Cell line models are essential tools to study the molecular mechanisms underlying tumor initiation and progression. There are limited treatment options for penile squamous cell carcinoma (PSCC), accounting for 1–2% of male tumors in developing countries, and limited progress in preclinical research in PSCC due to lacking available models with identified genomic characteristics. Here, biological and molecular characteristics and whole-genomic alterations were analyzed in a panel of PSCC cell lines newly established in our laboratory. These cell lines were all human papillomavirus (HPV)-negative, epithelial-like, immortalized, and tumorigenic in nude mice, whereas they displayed different proliferation, migration and invasion capacities in vitro, and tumorigenic ability in nude mice. They were all cisplatin sensitive, anti-EGFR therapy resistant, and androgen irresponsive. Whole-genomic sequecing analysis revealed that transition mutations (C:G>T:A and T:A>C:G) were the most common substitution types in these cell lines, whereas ERCC5, TP53, PTH1, CLTCL1, NOTCH2, MAP2K3, CDK11A/B, USP6, ADCH5, BCLAF1, CDKN2A, FANCD2, HRAS, and NOTCH1 were the most frequently altered genes. Amplifications of MYC, PLAG1, NCOA2, RUNX1T1, COX6C, and EGFR and losses of FBXW7, TET2, XPC, and FANCE were frequently observed in cell lines. The exomic variations between cell lines and their corresponding cancer tissues were highly consistent. Genetic variations were mainly involved in the MAPK, Jak-STAT, TGF-beta, Notch, and apoptosis signaling pathways. Conclusively, these panel of PSCC cell lines established in our laboratory harbor some common or specific biological characteristics and genomic variations, and they may serve as optimal models to investigate the molecular mechanisms underlying the progression, metastasis, relapses, and treatment resistance of PSCC and to develop effective treatment strategy.
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影响因子：
16.6
作者：
Domcke, Silvia;Sinha, Rileen;Levine, Douglas A.;Sander, Chris;Schultz, Nikolaus
通讯作者：
Schultz, Nikolaus
影响因子：
11.2
作者：
Feber A;Worth DC;Chakravarthy A;de Winter P;Shah K;Arya M;Saqib M;Nigam R;Malone PR;Tan WS;Rodney S;Freeman A;Jameson C;Wilson GA;Powles T;Beck S;Fenton T;Sharp TV;Muneer A;Kelly JD
通讯作者：
Kelly JD
影响因子：
5.8
作者：
Ali, Siraj M.;Pal, Sumanta K.;Miller, Vincent A.
通讯作者：
Miller, Vincent A.
具有有害 TP53 突变的阴茎癌细胞系 penl1 的建立和表征，作为 HPV 阴性阴茎癌发生的范例
影响因子：
--
作者：
Chen J;Yao K;Li Z;Deng C;Wang L;Yu X;Liang P;Xie Q;Chen P;Qin Z;Ye Y;Liu Z;Zhou F;Zhang Z;Han H
通讯作者：
Han H
影响因子：
64.8
作者：
Garnett, Mathew J.;Edelman, Elena J.;Heidorn, Sonja J.;Greenman, Chris D.;Dastur, Anahita;Lau, King Wai;Greninger, Patricia;Thompson, I. Richard;Luo, Xi;Soares, Jorge;Liu, Qingsong;Iorio, Francesco;Surdez, Didier;Chen, Li;Milano, Randy J.;Bignell, Graham R.;Tam, Ah T.;Davies, Helen;Stevenson, Jesse A.;Barthorpe, Syd;Lutz, Stephen R.;Kogera, Fiona;Lawrence, Karl;McLaren-Douglas, Anne;Mitropoulos, Xeni;Mironenko, Tatiana;Thi, Helen;Richardson, Laura;Zhou, Wenjun;Jewitt, Frances;Zhang, Tinghu;O'Brien, Patrick;Boisvert, Jessica L.;Price, Stacey;Hur, Wooyoung;Yang, Wanjuan;Deng, Xianming;Butler, Adam;Choi, Hwan Geun;Chang, JaeWon;Baselga, Jose;Stamenkovic, Ivan;Engelman, Jeffrey A.;Sharma, Sreenath V.;Delattre, Olivier;Saez-Rodriguez, Julio;Gray, Nathanael S.;Settleman, Jeffrey;Futreal, P. Andrew;Haber, Daniel A.;Stratton, Michael R.;Ramaswamy, Sridhar;McDermott, Ultan;Benes, Cyril H.
通讯作者：
Benes, Cyril H.