Laboratório de Cultura de Tecidos e Citogenética, SAMAM, Instituto Evandro Chagas, Ananindeua, PA, Brasil.
Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
Braz J Med Biol Res. 2021 Jan 15;54(3):e9571. doi: 10.1590/1414-431X20209571. eCollection 2021.
Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.
癌细胞系被广泛用作肿瘤发生的体外模型,促进了癌症生物学和转化医学的基础发现。目前,胶质母细胞瘤(GBM)的治疗选择很少,具有准确基因组和转录组特征的体外模型也有限。在这里,对一种新的 GBM 细胞系 AHOL1 进行了详细的特征描述,以便根据其核型、拷贝数改变(CNA)和转录组谱对其分子组成进行全面描述,然后验证与 GBM 肿瘤发生相关的关键因素。大量的 CNA 和差异表达基因(DEGs)被鉴定出来。CNA 分布在整个基因组中,包括 Xq11.1-q28、Xp22.33-p11.1、Xq21.1-q21.33、4p15.1-p14、8q23.2-q23.3 的增益和 Yq11.21-q12、Yp11.31-p11.2 和 15q11.1-q11.2 的缺失。鉴定出 9 个可用药基因,包括 HCRTR2、ETV1、PTPRD、PRKX、STS、RPS6KA6、ZFY、USP9Y 和 KDM5D。通过整合 DEGs 和 CNA,我们在 14 条通路中鉴定出 57 个重叠基因。通过 RT-qPCR 验证了 DEGs-CNA 数据集中发现的几个与癌症相关候选物的表达变化。总之,AHOL1 的这一首次全面基因组和转录组图谱为进一步研究提供了独特的资源,并确定了几个可能对 GBM 的治疗、生物学和分子研究有用的可用药靶标。