Genomics Underlying Familial Thyroid Carcinoma in Dogs

Abstract

Thyroid cancer is the most common endocrine neoplasm occurring in dogs. We reported familial thyroid follicular cell carcinomas (FCCs) in 54 Dutch German longhaired pointer (GLP) dogs. We investigated the genetics of the FCC in these dogs, including the germline risk mutations and somatic driver mutations. We identified the germline risk factor locating in the TPO gene for these hereditary FCCs through a combination of genome-wide association study (GWAS) and homozygosity mapping analyses using SNP array genotype data and whole-genome sequencing data. We further investigated the somatic mutation landscape of these FCCs using high-depth whole-genome sequencing technology of the tumors. A recurrent missense mutation in the GNAS gene was identified as a very promising driver mutation. We validated this somatic mutation using Sanger sequencing and revealed a prevalence of 62.5% among thyroid tumors identified in the Dutch GLPs. In addition, we can also review the findings in genetics of other canine thyroid tumors in recent years.