Canine osteosarcoma genome sequencing identifies recurrent mutations in DMD and the histone methyltransferase gene SETD2
Open accessAbstract
Osteosarcoma (OS) is a rare, metastatic, human adolescent cancer that also occurs in pet dogs. To define the genomic underpinnings of canine OS, we performed multi-platform analysis of OS tumors from 59 dogs, including whole genome sequencing (n = 24) and whole exome sequencing (WES;n = 13) of primary tumors and matched normal tissue, WES (n = 10) of matched primary/metastatic/normal samples and RNA sequencing (n = 54) of primary tumors. We found that canine OS recapitulates features of human OS including low point mutation burden (median 1.98 per Mb) with a trend towards higher burden in metastases, high structural complexity, frequent TP53(71%), PI3K pathway (37%), and MAPK pathway mutations (17%), and low expression of immune-associated genes. We also identified novel features of canine OS including putatively inactivating somatic SETD2(42%) and DMD(50%) aberrations. These findings set the stage for understanding OS development in dogs and humans, and establish genomic contexts for future comparative analyses.
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Canine osteosarcoma is very similar to the human disease in its histology, genetics, and clinical course, but it is much more common, with roughly 25,000 new cases annually.
“Canine osteosarcoma has histological, genetic and clinical features nearly identical to the human disease 232 but has a much higher incidence, with an estimated 25,000 new cases of canine disease occurring each year 232 .”
From Osteosarcoma (2022) · cites this paper as [232]
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Beird, H. C., Bielack, S. S., Flanagan, A. M., Gill, J., Heymann, D., Janeway, K. A., Livingston, J. A., Roberts, R. D., Strauss, S. J., & Gorlick, R. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00409-y · Cited by 660 · see citing works
Self-citation
- Authors
- Gardner, H. L., Sivaprakasam, K., Briones, N., Zismann, V., Perdigones, N., Drenner, K., Facista, S., Richholt, R., Liang, W., Aldrich, J., Trent, J. M., Shields, P. G., Robinson, N., Johnson, J., Lana, S., Houghton, P., Fenger, J., Lorch, G., Janeway, K. A., London, C. A., & Hendricks, W. P. D.
- Affiliations
- Tufts University (US)
- Translational Genomics Research Institute (US)
- The Ohio State University (US)
- Broad Institute (US)
- Colorado State University (US)
- The University of Texas at San Antonio Health Science Center (US)
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Hendricks, William P. D.
- ORCID
- Venue
- Communications Biology
- Published
- 2019-07-19
- Volume
- 2
- Issue
- 1
- Pages
- 266-266
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC6642146
- OpenAlex
- W2963498060
- Cited by
- 120
- References
- 82
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 18 · 2023: 25 · 2022: 16 · 2021: 24 · 2020: 14 · 2019: 4
- FWCI
- 10.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Dana-Farber/Harvard Cancer Center (P30CA006516, CA006516)
- National Institutes of Health (UL1TR002733, K01OD019923, CA 006516, CA016058)
- NIH Office of the Director (K01OD019923, P30 CA016058)
- National Cancer Institute (CA016058, P01CA165995, CA006516, P30CA016058, P30CA006516)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Veterinary Oncology Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- canine osteosarcoma, canine cancer, DMD gene mutations, SETD2, histone methyltransferase, somatic mutations, TP53, PI3K signaling, MAPK signaling, metastasis, comparative oncology
- MeSH terms
- Whole Genome Sequencing, Animals, Bone Neoplasms, Dogs, Mutation, Histone-Lysine N-Methyltransferase, Osteosarcoma, Dystrophin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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