Becker Aline P, Sells Blake E, Haque S Jaharul, Chakravarti Arnab
Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
St. Louis School of Medicine, St. Louis, MO 63310, USA.
Cancers (Basel). 2021 Feb 12;13(4):761. doi: 10.3390/cancers13040761.
One of the main reasons for the aggressive behavior of glioblastoma (GBM) is its intrinsic intra-tumor heterogeneity, characterized by the presence of clonal and subclonal differentiated tumor cell populations, glioma stem cells, and components of the tumor microenvironment, which affect multiple hallmark cellular functions in cancer. "Tumor Heterogeneity" usually encompasses both (population-level differences); and (differences within individual tumors). Tumor heterogeneity may be assessed in a single time point (spatial heterogeneity) or along the clinical evolution of GBM (longitudinal heterogeneity). Molecular methods may detect clonal and subclonal alterations to describe tumor evolution, even when samples from multiple areas are collected in the same time point (spatial-temporal heterogeneity). In GBM, although the inter-tumor mutational landscape is relatively homogeneous, intra-tumor heterogeneity is a striking feature of this tumor. In this review, we will address briefly the inter-tumor heterogeneity of the CNS tumors that yielded the current glioma classification. Next, we will take a deeper dive in the intra-tumor heterogeneity of GBMs, which directly affects prognosis and response to treatment. Our approach aims to follow technological developments, allowing for characterization of intra-tumor heterogeneity, beginning with differences on histomorphology of GBM and ending with molecular alterations observed at single-cell level.
胶质母细胞瘤（GBM）侵袭性的主要原因之一是其内在的肿瘤内异质性，其特征是存在克隆性和亚克隆性分化的肿瘤细胞群体、胶质瘤干细胞以及肿瘤微环境的组成部分，这些因素会影响癌症中多种标志性细胞功能。“肿瘤异质性”通常包括（群体水平差异）和（单个肿瘤内的差异）。肿瘤异质性可在单个时间点进行评估（空间异质性），也可根据GBM的临床进展进行评估（纵向异质性）。分子方法可检测克隆性和亚克隆性改变以描述肿瘤演变，即使在同一时间点收集多个区域的样本时也是如此（时空异质性）。在GBM中，尽管肿瘤间的突变图谱相对均匀，但肿瘤内异质性是这种肿瘤的一个显著特征。在本综述中，我们将简要讨论产生当前胶质瘤分类的中枢神经系统肿瘤的肿瘤间异质性。接下来，我们将更深入地探讨GBM的肿瘤内异质性，它直接影响预后和对治疗的反应。我们的方法旨在跟踪技术发展，以便从GBM组织形态学的差异开始，到单细胞水平观察到的分子改变结束，对肿瘤内异质性进行表征。
