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

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.

SUBMITTER: Gardner HL 

PROVIDER: S-EPMC6642146 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature