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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / veterinary*
  • Dogs
  • Dystrophin / genetics*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Mutation*
  • Osteosarcoma / genetics*
  • Osteosarcoma / veterinary*
  • Whole Genome Sequencing

Substances

  • Dystrophin
  • Histone-Lysine N-Methyltransferase