Genetic Resources Core Facility, Department of Genetic Medicine, Johns Hopkins University School of Medicine, 600 N. Wolfe St., 1034 Blalock, Baltimore, MD 21287, USA.
Department of Genetic Medicine, Johns Hopkins Genomics, Johns Hopkins University School of Medicine, 1812 Ashland Ave., Suite 200, Baltimore, MD 21205, USA.
Genes (Basel). 2024 Sep 26;15(10):1254. doi: 10.3390/genes15101254.
BACKGROUND/OBJECTIVES: The rat osteosarcoma cell line UMR-106 is widely used for the study of bone cancer biology but it has not been well characterized with modern genomic methods.
To better understand the biology of UMR-106 cells we used a combination of optical genome mapping (OGM), long-read sequencing nanopore sequencing and RNA sequencing.The UMR-106 genome was compared to a strain-matched Sprague-Dawley rat for variants associated with human osteosarcoma while expression data were contrasted with a public osteoblast dataset.
Using the COSMIC database to identify the most affected genes in human osteosarcomas we found somatic mutations in Tp53 and H3f3a. OGM identified a relatively small number of differences between the cell line and a strain-matched control animal but did detect a ~45 Mb block of amplification that included Myc on chromosome 7 which was confirmed by long-read sequencing. The amplified region showed several blocks of non-contiguous rearranged sequence implying complex rearrangements during their formation and included 14 genes reported as biomarkers in human osteosarcoma, many of which also showed increased transcription. A comparison of 5mC methylation from the nanopore reads of tumor and control samples identified genes with distinct differences including the OS marker Cdkn2a.
This dataset illustrates the value of long DNA methods for the characterization of cell lines and how inter-species analysis can inform us about the genetic nature underlying mutations that underpin specific tumor types. The data should be a valuable resource for investigators studying osteosarcoma, in general, and specifically the UMR-106 model.
背景/目的：大鼠骨肉瘤细胞系 UMR-106 广泛用于骨肉瘤生物学的研究，但尚未通过现代基因组方法进行充分表征。
为了更好地了解 UMR-106 细胞的生物学特性，我们结合光学基因组图谱（OGM）、长读长测序纳米孔测序和 RNA 测序技术。将 UMR-106 基因组与匹配的 Sprague-Dawley 大鼠进行比较，以确定与人类骨肉瘤相关的变体，同时将表达数据与公共成骨细胞数据集进行对比。
利用 COSMIC 数据库识别人类骨肉瘤中受影响最严重的基因，我们发现 Tp53 和 H3f3a 存在体细胞突变。OGM 鉴定出细胞系与匹配对照动物之间相对较少的差异，但确实检测到包括 7 号染色体上 Myc 在内的约 45 Mb 扩增块，这通过长读长测序得到了证实。扩增区域显示出几个不连续重排序列块，表明在其形成过程中发生了复杂的重排，其中包括 14 个被报道为人类骨肉瘤生物标志物的基因，许多基因的转录也增加了。来自肿瘤和对照样本的纳米孔读数的 5mC 甲基化比较鉴定出具有明显差异的基因，包括 OS 标志物 Cdkn2a。
该数据集说明了长 DNA 方法对细胞系进行特征描述的价值，以及种间分析如何为基础突变提供遗传性质提供信息，这些突变是特定肿瘤类型的基础。该数据集应该是研究骨肉瘤的研究人员的宝贵资源，特别是 UMR-106 模型。
