Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Nat Commun. 2022 Apr 19;13(1):2144. doi: 10.1038/s41467-022-29794-4.
Access to clinically relevant small cell lung cancer (SCLC) tissue is limited because surgical resection is rare in metastatic SCLC. Patient-derived xenografts (PDX) and circulating tumor cell-derived xenografts (CDX) have emerged as valuable tools to characterize SCLC. Here, we present a resource of 46 extensively annotated PDX/CDX models derived from 33 patients with SCLC. We perform multi-omic analyses, using targeted tumor next-generation sequencing, RNA-sequencing, and immunohistochemistry to deconvolute the mutational landscapes, global expression profiles, and molecular subtypes of these SCLC models. SCLC subtypes characterized by transcriptional regulators, ASCL1, NEUROD1 and POU2F3 are confirmed in this cohort. A subset of SCLC clinical specimens, including matched PDX/CDX and clinical specimen pairs, confirm that the primary features and genomic and proteomic landscapes of the tumors of origin are preserved in the derivative PDX models. This resource provides a powerful system to study SCLC biology.
获得具有临床相关性的小细胞肺癌 (SCLC) 组织受到限制，因为转移性 SCLC 很少进行手术切除。患者来源的异种移植物 (PDX) 和循环肿瘤细胞来源的异种移植物 (CDX) 已成为描述 SCLC 的有价值的工具。在这里，我们提供了 46 种经过广泛注释的源自 33 名 SCLC 患者的 PDX/CDX 模型的资源。我们使用靶向肿瘤下一代测序、RNA 测序和免疫组织化学进行多组学分析，以剖析这些 SCLC 模型的突变景观、全局表达谱和分子亚型。在该队列中证实了以转录调节剂 ASCL1、NEUROD1 和 POU2F3 为特征的 SCLC 亚型。一部分 SCLC 临床标本，包括匹配的 PDX/CDX 和临床标本对，证实了起源肿瘤的主要特征以及基因组和蛋白质组景观在衍生的 PDX 模型中得以保留。该资源提供了一个强大的系统来研究 SCLC 生物学。
