Patient Derived Xenograft for Delivery of Precision Medicine in Castrate Resistant Prostate Cancer. Homo sapiens

Developing animal models representating the cancer biology of advanced prostate cancer patients is challenging but essential for delivering individualized medical therapies. In an effort to develop patient derived xenograft (PDX) models, we took the metastatic site tissue from the rib lesion twice (ie, before and after enzalutamide treatment) over a twelve week period and implanted subcutaneously and under the renal capsule in immuno-deficient mice. To characterize and compare the genome and transcriptome landscapes of patient tumor tissues and the corresponding PDX models, we performed whole exome and transcriptome sequencing for metastatic tumor tissue as well as its derived PDXs. We demonstrated the feasibility of developping PDX models from patient who developed castrate-resistant prostate cancer. Our data suggested PDX models preserve the patient’s genomic and transcriptomic alterations in high fidelity, as illustrated by somatic mutation, copy number variation, gene fusion and gene expression. Overall design: RNA sequencing of prostate cancer tumor tissue and derived xenograft using Illumina HiSeq 2000.

构建能够复现晚期前列腺癌患者肿瘤生物学特征的动物模型颇具挑战，但对于实现个体化医疗治疗而言至关重要。为构建患者来源异种移植瘤（patient derived xenograft, PDX）模型，我们在12周周期内两次采集了肋骨转移灶组织样本（分别于恩扎卢胺治疗前及治疗后），并将其分别皮下移植与肾包膜下移植至免疫缺陷小鼠体内。为表征并对比患者肿瘤组织及其对应PDX模型的基因组与转录组特征图谱，我们对转移瘤组织及其衍生的PDX模型开展了全外显子组测序与转录组测序。本研究证实了从去势抵抗性前列腺癌患者体内构建PDX模型的可行性。研究数据表明，PDX模型可高保真保留患者的基因组与转录组改变，这一点可通过体细胞突变、拷贝数变异、基因融合及基因表达特征得到验证。实验整体设计：采用Illumina HiSeq 2000平台对前列腺癌肿瘤组织及其衍生异种移植瘤开展RNA测序。