当前位置：
X-MOL 学术
›
Cell Stem Cell
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2018-Dec-06 , DOI: 10.1016/j.stem.2018.09.016 Helen H N Yan 1 , Hoi Cheong Siu 1 , Simon Law 2 , Siu Lun Ho 1 , Sarah S K Yue 1 , Wai Yin Tsui 1 , Dessy Chan 1 , April S Chan 1 , Stephanie Ma 3 , Ka On Lam 4 , Sina Bartfeld 5 , Alice H Y Man 1 , Bernard C H Lee 1 , Annie S Y Chan 1 , Jason W H Wong 3 , Priscilla S W Cheng 1 , Anthony K W Chan 1 , Jiangwen Zhang 6 , Jue Shi 7 , Xiaodan Fan 8 , Dora L W Kwong 4 , Tak W Mak 9 , Siu Tsan Yuen 10 , Hans Clevers 11 , Suet Yi Leung 12
Cell Stem Cell ( IF 19.8 ) Pub Date : 2018-Dec-06 , DOI: 10.1016/j.stem.2018.09.016 Helen H N Yan 1 , Hoi Cheong Siu 1 , Simon Law 2 , Siu Lun Ho 1 , Sarah S K Yue 1 , Wai Yin Tsui 1 , Dessy Chan 1 , April S Chan 1 , Stephanie Ma 3 , Ka On Lam 4 , Sina Bartfeld 5 , Alice H Y Man 1 , Bernard C H Lee 1 , Annie S Y Chan 1 , Jason W H Wong 3 , Priscilla S W Cheng 1 , Anthony K W Chan 1 , Jiangwen Zhang 6 , Jue Shi 7 , Xiaodan Fan 8 , Dora L W Kwong 4 , Tak W Mak 9 , Siu Tsan Yuen 10 , Hans Clevers 11 , Suet Yi Leung 12
Affiliation
|
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.
中文翻译：
全面的人类胃癌类器官生物库可捕获肿瘤亚型异质性，并能进行治疗筛选。
胃癌表现出明显的分子异质性，具有侵略性和抗药性。因此，为精确医学开发迫切需要包含独特亚型的良好体外模型。在这里，我们建立了一个原发性胃癌类器官（GCO）生物库，该库包含来自34位患者的正常，异常增生，癌症和淋巴结转移（n = 63），包括详细的全外显子组和转录组分析。该队列涵盖最已知的分子亚型（包括EBV，MSI，肠/ CIN和弥漫性/ GS，具有CLDN18-ARHGAP6或CTNND1-ARHGAP26融合或RHOA突变），捕获区域异质性和亚克隆结构，同时捕获其形态，转录组和即使经过长期培养，基因组图谱仍与体内肿瘤极为相似。大规模药物筛选显示了对最近批准或临床试验中未曾预料到的药物的敏感性，这些药物包括纳帕布辛，Abemaciclib和ATR抑制剂VE-822。总体而言，这种新的GCO生物库具有链接的基因组数据，为研究癌细胞生物学和精确的癌症治疗提供了有用的资源。
更新日期：2018-10-19
中文翻译：
全面的人类胃癌类器官生物库可捕获肿瘤亚型异质性，并能进行治疗筛选。
胃癌表现出明显的分子异质性，具有侵略性和抗药性。因此，为精确医学开发迫切需要包含独特亚型的良好体外模型。在这里，我们建立了一个原发性胃癌类器官（GCO）生物库，该库包含来自34位患者的正常，异常增生，癌症和淋巴结转移（n = 63），包括详细的全外显子组和转录组分析。该队列涵盖最已知的分子亚型（包括EBV，MSI，肠/ CIN和弥漫性/ GS，具有CLDN18-ARHGAP6或CTNND1-ARHGAP26融合或RHOA突变），捕获区域异质性和亚克隆结构，同时捕获其形态，转录组和即使经过长期培养，基因组图谱仍与体内肿瘤极为相似。大规模药物筛选显示了对最近批准或临床试验中未曾预料到的药物的敏感性，这些药物包括纳帕布辛，Abemaciclib和ATR抑制剂VE-822。总体而言，这种新的GCO生物库具有链接的基因组数据，为研究癌细胞生物学和精确的癌症治疗提供了有用的资源。
京公网安备 11010802027423号