PDF(Pubmed)
Abstract：
Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling.
摘要：
患者来源的异种移植（PDX）模型广泛用于癌症研究。探讨非小细胞肺癌PDX模型的基因组保真度,我们从参加TRACERx研究的22例患者中建立了48个PDX模型.多区域肿瘤取样增加了成功的PDX植入,并且大多数模型在组织学上与其母体肿瘤相似。全外显子组测序能够比较肿瘤和PDX模型，我们提供了一种适应的小鼠参考基因组，用于改善从测序数据中去除NODscidgamma（NSG）小鼠衍生的读数。PDX模型的建立造成了基因组瓶颈,模型通常代表单个肿瘤亚克隆。虽然在来自同一肿瘤的独立模型中代表了不同的肿瘤亚克隆，单个PDX模型未完全概括肿瘤内异质性.小鼠中持续的基因组进化对肿瘤和PDX模型之间的基因组距离贡献不大。我们的研究强调了使用PDX模型时考虑原发性肿瘤异质性的重要性，并强调了全面肿瘤采样的益处。
