LeBlanc Véronique G, Trinh Diane L, Aslanpour Shaghayegh, Hughes Martha, Livingstone Dorothea, Jin Dan, Ahn Bo Young, Blough Michael D, Cairncross J Gregory, Chan Jennifer A, Kelly John J P, Marra Marco A
Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, V5Z 4S6 BC, Canada.
Department of Clinical Neurosciences, University of Calgary, Calgary, T2N 2T9 AB, Canada; Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, T2N 4Z6 AB, Canada.
Cancer Cell. 2022 Apr 11;40(4):379-392.e9. doi: 10.1016/j.ccell.2022.02.016. Epub 2022 Mar 17.
Glioblastomas (GBMs) are aggressive brain tumors characterized by extensive inter- and intratumor heterogeneity. Patient-derived models, such as organoids and explants, have recently emerged as useful models to study such heterogeneity, although the extent to which they can recapitulate GBM genomic features remains unclear. Here, we analyze bulk exome and single-cell genome and transcriptome profiles of 12 IDH wild-type GBMs, including two recurrent tumors, and of patient-derived explants (PDEs) and gliomasphere (GS) lines derived from these tumors. We find that PDEs are genetically similar to, and variably retain gene expression characteristics of, their parent tumors. Notably, PDEs appear to exhibit similar levels of transcriptional heterogeneity compared with their parent tumors, whereas GS lines tend to be enriched for cells in a more uniform transcriptional state. The approaches and datasets introduced here will provide a valuable resource to help guide experiments using GBM-derived models, especially in the context of studying cellular heterogeneity.
胶质母细胞瘤（GBM）是侵袭性脑肿瘤，其特征在于肿瘤间和肿瘤内存在广泛的异质性。患者来源的模型，如类器官和外植体，最近已成为研究这种异质性的有用模型，尽管它们能够重现GBM基因组特征的程度仍不清楚。在这里，我们分析了12个异柠檬酸脱氢酶（IDH）野生型GBM（包括两个复发性肿瘤）以及源自这些肿瘤的患者来源外植体（PDE）和胶质瘤球（GS）系的全外显子组、单细胞基因组和转录组图谱。我们发现，PDE在基因上与其亲本肿瘤相似，并可变地保留其亲本肿瘤的基因表达特征。值得注意的是，与亲本肿瘤相比，PDE似乎表现出相似水平的转录异质性，而GS系往往富含处于更均匀转录状态的细胞。本文介绍的方法和数据集将提供宝贵的资源，以帮助指导使用GBM衍生模型的实验，特别是在研究细胞异质性的背景下。
