4.6 Article

The genomic landscape of canine osteosarcoma cell lines reveals conserved structural complexity and pathway alterations

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PLOS ONE
卷 17, 期 9, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0274383

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资金

  1. National Cancer Institute of the National Institutes of Health [F32CA247088]
  2. National Institutes of Health [P01CA165995, K01OD028268, R37CA218570, R01CA255319]
  3. Morris Animal Foundation [D21CA-026]
  4. American Kennel Club Canine Health Foundation [02768]

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The whole genome characterization of canine osteosarcoma cell lines reveals that many alterations previously characterized in primary canine osteosarcoma tissue are also present in these cell lines. This provides a new framework for incorporating in vitro findings into the design of future clinical studies on spontaneous canine osteosarcoma.
The characterization of immortalized canine osteosarcoma (OS) cell lines used for research has historically been based on phenotypic features such as cellular morphology and expression of bone specific markers. With the increasing use of these cell lines to investigate novel therapeutic approaches prior to in vivo translation, a much more detailed understanding regarding the genomic landscape of these lines is required to ensure accurate interpretation of findings. Here we report the first whole genome characterization of eight canine OS cell lines, including single nucleotide variants, copy number variants and other structural variants. Many alterations previously characterized in primary canine OS tissue were observed in these cell lines, including TP53 mutations, MYC copy number gains, loss of CDKN2A, PTEN, DLG2, MAGI2, and RB1 and structural variants involving SETD2, DLG2 and DMD. These data provide a new framework for understanding how best to incorporate in vitro findings generated using these cell lines into the design of future clinical studies involving dogs with spontaneous OS.

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