Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
Cell Stem Cell. 2018 Dec 6;23(6):882-897.e11. doi: 10.1016/j.stem.2018.09.016. Epub 2018 Oct 18.
Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (n = 63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.
胃癌表现出明显的分子异质性，具有侵袭性和治疗耐药性。因此，迫切需要涵盖独特亚型的良好的体外模型来进行精准医学的发展。在这里，我们建立了一个包含 34 名患者的原发性胃癌类器官（GCO）生物库，其中包括正常、发育不良、癌症和淋巴结转移（n=63），并进行了详细的全外显子组和转录组分析。该队列包含了大多数已知的分子亚型（包括 EBV、MSI、肠型/CIN 和弥漫型/GS，以及 CLDN18-ARHGAP6 或 CTNND1-ARHGAP26 融合或 RHOA 突变），同时还能捕获区域性异质性和亚克隆结构，其形态、转录组和基因组图谱在长期培养后仍与体内肿瘤密切相似。大规模药物筛选揭示了对最近批准或临床试验中的意外药物的敏感性，包括 Napabucasin、Abemaciclib 和 ATR 抑制剂 VE-822。总的来说，这个新的 GCO 生物库及其相关的基因组数据为研究癌症细胞生物学和精准癌症治疗提供了一个有用的资源。
