Lozano-Ureña Anna, Jiménez-Villalba Esteban, Pinedo-Serrano Alejandro, Jordán-Pla Antonio, Kirstein Martina, Ferrón Sacri R
Instituto de Biotecnología y Biomedicina (BIOTECMED), Valencia, Spain.
Departamento de Biología Celular, Universidad de Valencia, Valencia, Spain.
Front Oncol. 2021 Mar 12;11:630482. doi: 10.3389/fonc.2021.630482. eCollection 2021.
In human glioblastoma (GBM), the presence of a small population of cells with stem cell characteristics, the glioma stem cells (GSCs), has been described. These cells have GBM potential and are responsible for the origin of the tumors. However, whether GSCs originate from normal neural stem cells (NSCs) as a consequence of genetic and epigenetic changes and/or dedifferentiation from somatic cells remains to be investigated. Genomic imprinting is an epigenetic marking process that causes genes to be expressed depending on their parental origin. The dysregulation of the imprinting pattern or the loss of genomic imprinting (LOI) have been described in different tumors including GBM, being one of the earliest and most common events that occurs in human cancers. Here we have gathered the current knowledge of the role of imprinted genes in normal NSCs function and how the imprinting process is altered in human GBM. We also review the changes at particular imprinted loci that might be involved in the development of the tumor. Understanding the mechanistic similarities in the regulation of genomic imprinting between normal NSCs and GBM cells will be helpful to identify molecular players that might be involved in the development of human GBM.
在人类胶质母细胞瘤（GBM）中，已发现存在一小部分具有干细胞特征的细胞，即胶质瘤干细胞（GSCs）。这些细胞具有引发GBM的潜能，是肿瘤的起源细胞。然而，GSCs是否源于正常神经干细胞（NSCs），是基因和表观遗传变化的结果，还是体细胞去分化的结果，仍有待研究。基因组印记是一种表观遗传标记过程，它使基因根据其亲本来源进行表达。印记模式失调或基因组印记丢失（LOI）已在包括GBM在内的不同肿瘤中被描述，这是人类癌症中最早且最常见的事件之一。在此，我们收集了目前关于印记基因在正常NSCs功能中的作用以及印记过程在人类GBM中如何改变的知识。我们还回顾了可能与肿瘤发生有关的特定印记位点的变化。了解正常NSCs和GBM细胞之间基因组印记调控的机制相似性，将有助于识别可能参与人类GBM发生发展的分子因子。
