Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
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DOI：
10.1371/journal.pone.0103988
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Helleman J
中科院分区：
文献类型：
--
作者：
Beaufort CM;Helmijr JC;Piskorz AM;Hoogstraat M;Ruigrok-Ritstier K;Besselink N;Murtaza M;van IJcken WF;Heine AA;Smid M;Koudijs MJ;Brenton JD;Berns EM;Helleman J
上皮性卵巢癌是一种高度异质性的疾病，在西方世界仍然是最致命的妇科恶性肿瘤。治疗方法需要考虑患者间和肿瘤内的异质性，并且代表不同组织学和分子卵巢癌亚型的体外模型的详细特征对于实现可靠的临床前测试至关重要。大约有100种公开的卵巢癌细胞系，但它们的细胞和分子特征在很大程度上是未被描述的。我们对39种卵巢癌细胞系在统一条件下的生长特征、mRNA/microRNA表达、外显子测序、临床相关治疗药物反应进行了表征，并整理了所有关于原始临床特征和起源部位的可用信息。我们测试了细胞和分子特征与临床特征之间的统计关联。39株卵巢癌细胞系中，14株为高级别浆液型，4株为浆液型，1株为低级别浆液型，20株为非浆液型。三种形态亚型：上皮（n = 21），圆形（n = 7）和梭形（n = 12），显示出不同的生物学和分子特征，包括梭形亚型中细胞运动和迁移相关基因的过表达。与原始临床资料比较，纺锤样肿瘤与转移、晚期、次优减容和预后不良有关。此外，纺锤形、圆形和上皮形态的表达谱分别与先前描述的c1 -间质、c5 -间质和C4卵巢亚型表达谱聚集。39种卵巢癌细胞系在受控、统一的条件下的综合分析显示了临床相关的细胞和基因组特征。这些数据为卵巢癌的组织学和分子亚型选择模型制定特异性治疗方法提供了合理的依据。
Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological and molecular ovarian cancer subtypes is critical to enable reliable preclinical testing. There are approximately 100 publicly available ovarian cancer cell lines but their cellular and molecular characteristics are largely undescribed. We have characterized 39 ovarian cancer cell lines under uniform conditions for growth characteristics, mRNA/microRNA expression, exon sequencing, drug response for clinically-relevant therapeutics and collated all available information on the original clinical features and site of origin. We tested for statistical associations between the cellular and molecular features of the lines and clinical features. Of the 39 ovarian cancer cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes: Epithelial (n = 21), Round (n = 7) and Spindle (n = 12) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes in the Spindle subtype. Comparison with the original clinical data showed association of the spindle-like tumours with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the expression profiles of Spindle, Round and Epithelial morphologies clustered with the previously described C1-stromal, C5-mesenchymal and C4 ovarian subtype expression profiles respectively. Comprehensive profiling of 39 ovarian cancer cell lines under controlled, uniform conditions demonstrates clinically relevant cellular and genomic characteristics. This data provides a rational basis for selecting models to develop specific treatment approaches for histological and molecular subtypes of ovarian cancer.
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影响因子：
24.3
作者：
Correia, Ana Luisa;Bissell, Mina J.
通讯作者：
Bissell, Mina J.
影响因子：
7.3
作者：
Ahmed, Ashour Ahmed;Etemadmoghadam, Dariush;Temple, Jillian;Lynch, Andy G.;Riad, Mohamed;Sharma, Raghwa;Stewart, Colin;Fereday, Sian;Caldas, Carlos;DeFazio, Anna;Bowtell, David;Brenton, James D.
通讯作者：
Brenton, James D.
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：
8.4
作者：
Banerjee, Susana;Kaye, Stan
通讯作者：
Kaye, Stan
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.