Gene expression data comparing Wilms tumor primary samples to patient-derived xenografts. Gene expression data comparing Wilms tumor primary samples to patient-derived xenografts

The lack of model systems limits the preclinical testing of novel therapies to address Wilms tumor patient groups with poor outcomes. Therefore, we established 45 heterotopic Wilms tumor patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). These WTPDX include six showing diffuse anaplasia, nine from patients who went on to experience disease relapse, and thirteen from patients with bilateral disease. WTPDX retained the genetic alterations and the global transcriptomic and methylation profile of corresponding primary WT. In addition, favorable histology WTPDX were chemosensitive, while unfavorable histology WTPDX were resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool for the testing of novel targeted therapies in the era of precision medicine. Overall design: Total RNA was extracted from 16 selected Wilms tumor patient-derived xenografts, 13 available corresponding primary tumor specimens, and three normal kidney specimens using the Qiagen RNeasy Midi kit (Qiagen, Hilden, Germany). Commercially available pooled total RNA from four human fetal kidneys was also included (Takara, Kusatsu, Japan).

缺乏合适的模型系统，限制了针对预后不良肾母细胞瘤（Wilms tumor, 以下简称WT）患者群体的新型疗法临床前测试。为此，我们在CB17 scid-/-免疫缺陷小鼠中构建了45株异位WT患者来源异种移植瘤（Wilms tumor patient-derived xenografts, 以下简称WTPDX），该模型体系可复现WT的生物学异质性。该批WTPDX包含6株携带弥漫性间变特征、9株来自后续出现疾病复发的患者，以及13株来自双侧病变的WT患者的移植瘤。WTPDX可保留对应原发性WT的遗传变异、全转录组及甲基化谱特征。此外，组织学类型良好的WTPDX对化疗敏感，而组织学类型不良的WTPDX则对长春新碱、放线菌素D及多柔比星组成的常规化疗方案耐药。本WTPDX文库是一项独特的科学资源，可复现WT的全部生物学异质性，为精准医学时代新型靶向疗法的测试提供了不可或缺的工具。
实验整体设计：使用Qiagen RNeasy 中量总RNA提取试剂盒（Qiagen，德国希尔德），从16株筛选后的WTPDX、13份可获取的对应原发性WT标本以及3份正常肾脏标本中提取总RNA；同时纳入了市售的4名人胎儿肾脏混合总RNA（Takara，日本滋贺县）。