A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity
A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity
复制标题
DOI：
10.1016/j.cell.2017.11.010
复制
发表时间：
2018-01-11
期刊：
影响因子：
64.5
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
--
作者：
Sachs, Norman;de Ligt, Joep;Clevers, Hans
乳腺癌（BC）包括多种不同的亚型，这些亚型在遗传、病理和临床上都存在差异。在这里，我们描述了一个强大的方案，长期培养人类乳腺上皮类器官。使用该方案，产生了bbb100原发和转移性BC类器官系，广泛概括了该疾病的多样性。BC类器官形态通常与原肿瘤的组织病理学、激素受体状态和HER2状态相匹配。DNA拷贝数变化和序列变化在肿瘤-类器官对中是一致的，即使在延长传代后也在很大程度上保持不变。BC类器官进一步填充了所有主要的基于基因表达的分类组，并允许体外药物筛选，与体内异种移植和患者反应一致。本研究描述了可用于癌症研究和药物开发的具有代表性的具有良好特征的BC类器官，以及以个性化方式评估体外药物反应的策略。
Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene-expression-based classification groups and allowed in vitro drug screens that were consistent with in vivo xeno-transplantations and patient response. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion.