ABSTRACT

One caveat in cancer research is the dependence of certain experimental systems that might not really reflect the properties of the primary tumours. The recent irruption of 3D cultured cells termed organoids could render a better representation of the original tumour sample. However, every laboratory has its own protocol and tissue-provider to establish these cancer models, preventing further dissemination and validation of the obtained data. To address this problem, the Human Cancer Models Initiative (HCMI) has selected the American Type Culture Collection (ATCC) to make available organoid models to the scientific community. In this regard, no epigenetic information is available for these samples and, overall, the DNA methylation profiles of human cancer organoids are largely unknown. Herein, we provide the DNA methylation landscape of 25 human cancer organoids available at the ATCC using a microarray that interrogates more than 850,000 CpG sites. We observed that the studied organoids retain the epigenetic setting of their original primary cancer type; that exhibit a DNA methylation landscape characteristic of transformed tissues excluding an overgrowth of normal-matched cells; and that are closer to the DNA methylation profiles of the corresponding primary tumours than to established 2D cell lines. Most importantly, the obtained DNA methylation results are freely available to everyone for further data mining. Thus, our findings support from the epigenetic standpoint that the ATCC human cancer organoids recapitulate many of the features of the disorder in the patient and are excellent tools to be shared among investigators for further tumour biology research.

摘要

癌症研究中的一个警告是某些实验系统的依赖性可能无法真正反映原发性肿瘤的特性。最近被称为类器官的3D培养细胞的破裂可以更好地代表原始肿瘤样品。但是，每个实验室都有自己的方案和组织提供者来建立这些癌症模型，从而阻止了进一步传播和验证所获得的数据。为了解决这个问题，人类癌症模型倡议（HCMI）选择了美国典型培养物保藏中心（ATCC），以向科学界提供类器官模型。在这方面，没有关于这些样品的表观遗传学信息，并且总体上，人类癌症类器官的DNA甲基化谱图很大程度上是未知的。在这里 我们使用可查询超过850,000个CpG位点的微阵列，提供了ATCC处可用的25种人类癌症类器官的DNA甲基化图谱。我们观察到，所研究的类器官保留了其原始原发癌类型的表观遗传背景。除正常匹配细胞的过度生长外，还具有转化组织的DNA甲基化景观特征；与建立的2D细胞系相比，更接近相应原发肿瘤的DNA甲基化分布。最重要的是，每个人都可以免费获得获得的DNA甲基化结果，以进行进一步的数据挖掘。从而，