Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumours in patients.
Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumours in patients.
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DOI：
10.1002/path.2929
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发表时间：
2011-10
影响因子：
7.3
通讯作者：
Signoretti, Sabina
中科院分区：
文献类型：
--
作者：
Grisanzio, Chiara;Seeley, Apryle;Chang, Michelle;Collins, Michael;Di Napoli, Arianna;Cheng, Su-Chun;Percy, Andrew;Beroukhim, Rameen;Signoretti, Sabina
肾细胞癌(RCC)是一种对现有治疗反应有限的侵袭性恶性肿瘤。包括肾细胞癌在内的人类癌症的体内模型对于开发更有效的治疗方法至关重要。不幸的是，目前的RCC模型不能准确地代表人类疾病的相关特性。本研究的目的是为临床前研究开发与临床相关的肾癌动物模型。我们将完整的人类肿瘤组织片段原位移植到免疫缺陷小鼠体内。通过比较移植前后肾脏肿瘤组织的形态、表型和遗传特征来验证移植的有效性。将20个肾肿瘤移植到小鼠体内。19例(95%)肿瘤生长成功。所有病例移植瘤和原发肿瘤的组织病理学和免疫表型特征基本一致。对10个病例的遗传改变的评估表明，移植物在很大程度上保留了植入前肾癌组织的遗传特征。事实上，原发肿瘤和相应的移植物显示出相同的VHL突变。10例中有6例(60%)DNA拷贝扩增或缺失模式相同。综上所述，肾细胞癌组织片段原位移植可以成功地用于建立与患者肾细胞癌相似的动物模型。这些模型对于体内的临床前药物测试以及对肾癌发生的深入了解将是非常有价值的。
Renal cell carcinoma (RCC) is an aggressive malignancy with limited responsiveness to existing treatments. In vivo models of human cancer, including RCC, are critical for developing more effective therapies. Unfortunately, current RCC models do not accurately represent relevant properties of the human disease. The goal of this study was to develop clinically relevant animal models of RCC for preclinical investigations. We transplanted intact human tumor tissue fragments orthotopically in immunodeficient mice. The xenografts were validated by comparing the morphologic, phenotypic, and genetic characteristics of the kidney tumor tissues before and after implantation. Twenty kidney tumors were transplanted into mice. Successful tumor growth was detected in 19 cases (95%). The histopathologic and immunophenotypic features of the xenografts and those of the original tumors largely overlapped in all the cases. Evaluation of genetic alterations in a subset of 10 cases demonstrated that the grafts largely retained the genetic features of the pre-implantation RCC tissues. Indeed, primary tumors and corresponding grafts displayed identical VHL mutations. Moreover, an identical pattern of DNA copy amplification or loss was observed in 6 of 10 cases (60%). In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients. These models will be invaluable for in vivo preclinical drug testing, and for deeper understanding of kidney carcinogenesis.
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影响因子：
254.7
作者：
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通讯作者：
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影响因子：
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