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人类癌症类器官在美国模式培养物集存库中的 DNA 甲基化图谱。

The DNA methylation landscape of human cancer organoids available at the American type culture collection.

机构信息

Josep Carreras Leukaemia Research Institute (IJC), Badalona , Barcelona, Spain.

Institucio Catalana de Recerca i Estudis Avançats (ICREA) , Barcelona, Spain.

出版信息

Epigenetics. 2020 Nov;15(11):1167-1177. doi: 10.1080/15592294.2020.1762398. Epub 2020 May 12.

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

癌症研究中有一个注意事项,即某些实验系统可能并不真正反映原发性肿瘤的特性,这取决于它们的依赖性。最近,所谓的 3D 培养细胞类器官的突然出现,可以更好地代表原始肿瘤样本。然而,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,这阻碍了获得的数据的进一步传播和验证。为了解决这个问题,人类癌症模型倡议(HCMI)选择了美国模式培养物集存库(ATCC),将类器官模型提供给科学界。在这方面,这些样本没有表观遗传信息,总的来说,人类癌症类器官的 DNA 甲基化图谱在很大程度上是未知的。在此,我们使用微阵列提供了 ATCC 提供的 25 个人类癌症类器官的 DNA 甲基化图谱,该微阵列检测了超过 850,000 个 CpG 位点。我们观察到,所研究的类器官保留了其原始原发性癌症类型的表观遗传设置;表现出转化组织的 DNA 甲基化特征,排除了正常匹配细胞的过度生长;并且与相应的原发性肿瘤的 DNA 甲基化图谱比与已建立的 2D 细胞系更接近。最重要的是,获得的 DNA 甲基化结果可供所有人免费用于进一步的数据挖掘。因此,我们的研究结果从表观遗传角度支持 ATCC 人类癌症类器官再现了患者疾病的许多特征,并且是研究人员之间共享以进行进一步肿瘤生物学研究的极好工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e590/7595613/2de3e70b2552/KEPI_A_1762398_F0001_C.jpg

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