Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Cell Rep. 2021 Nov 23;37(8):110055. doi: 10.1016/j.celrep.2021.110055.
Renal cell carcinoma (RCC) encompasses a heterogenous group of tumors, but representative preclinical models are lacking. We previously showed that patient-derived tumorgraft (TG) models recapitulate the biology and treatment responsiveness. Through systematic orthotopic implantation of tumor samples from 926 ethnically diverse individuals into non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice, we generate a resource comprising 172 independently derived, stably engrafted TG lines from 148 individuals. TG lines are characterized histologically and genomically (whole-exome [n = 97] and RNA [n = 102] sequencing). The platform features a variety of histological and oncogenotypes, including TCGA clades further corroborated through orthogonal metabolomic analyses. We illustrate how it enables a deeper understanding of RCC biology; enables the development of tissue- and imaging-based molecular probes; and supports advances in drug development.
肾细胞癌 (RCC) 包含一组异质性肿瘤，但代表性的临床前模型却缺乏。我们之前曾表明，患者来源的肿瘤移植 (TG) 模型再现了肿瘤的生物学特性和治疗反应性。通过对 926 名不同种族个体的肿瘤样本进行系统的原位移植到非肥胖型糖尿病 (NOD)/严重联合免疫缺陷 (SCID) 小鼠中，我们生成了一个包含 148 名个体的 172 个独立衍生、稳定植入的 TG 系的资源。TG 系在组织学和基因组学上具有特征 (全外显子 [n = 97] 和 RNA [n = 102] 测序)。该平台具有多种组织学和致癌基因型，包括通过正交代谢组学分析进一步证实的 TCGA 分支。我们举例说明了它如何能够更深入地了解 RCC 生物学；能够开发基于组织和成像的分子探针；并支持药物开发的进展。
