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Commun Biol. 2019 Jul 19;2:266. doi: 10.1038/s42003-019-0487-2. eCollection 2019.

Canine osteosarcoma genome sequencing identifies recurrent mutations in DMD and the histone methyltransferase gene SETD2.

Author information

1
1Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 USA.
2
2Translational Genomics Research Institute, Phoenix, AZ 85004 USA.
3
3College of Medicine, The Ohio State University, Columbus, OH 43210 USA.
4
4Cummings School of Veterinary Medicine, Tufts University, Grafton, MA 01536 USA.
5
5Broad Institute, Cambridge, MA 02142 USA.
6
6Colorado State University, Fort Collins, CO 80525 USA.
7
7University of Texas Health Science Center, San Antonio, TX 78229 USA.
8
8Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH 43210 USA.
9
9Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215 USA.
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Contributed equally

Abstract

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.

KEYWORDS:

Bone cancer; Cancer genomics; Dog; Sarcoma

Conflict of interest statement

Competing interestsK.A.J. has received research funding from Amgen and Pfizer, and travel support from Loxo. C.A.L. has performed consulting work for The One Health Company, Anivive, Karyopharm therapeutics, Zoetis, and Blue Buffalo. W.P.D.H. has performed consulting work for The One Health Company, received research funding from Ethos Veterinary Health, and received travel support from Pathway Vet Alliance. The other authors declare no competing interests.

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