Characterization of the Rat Osteosarcoma Cell Line UMR-106 by Long-Read Technologies Identifies a Large Block of Amplified Genes Associated with Human Disease

Genes (Basel). 2024 Sep 26;15(10):1254. doi: 10.3390/genes15101254.

Abstract

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.

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.

Results: 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.

Conclusions: 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.

Keywords: Myc amplification; nanopore sequencing; optical mapping; osteosarcoma.

MeSH terms

  • Animals
  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / pathology
  • Cell Line, Tumor
  • Chromosome Mapping
  • DNA Methylation / genetics
  • Gene Amplification
  • Humans
  • Mutation
  • Nanopore Sequencing / methods
  • Osteosarcoma* / genetics
  • Osteosarcoma* / pathology
  • Rats
  • Rats, Sprague-Dawley