Familial thyroid follicular cell carcinomas in a large number of Dutch German longhaired pointers

Abstract

Thyroid carcinomas originating from follicular cells of the thyroid gland occur in both humans and dogs and they have highly similar histomorphologic patterns. In dogs, thyroid carcinomas have not been extensively investigated, especially concerning the familial origin of thyroid carcinomas. Here we report familial thyroid follicular cell carcinomas confirmed by histology in 54 Dutch origin German longhaired pointers. From the pedigree, 45 of 54 histopathologically confirmed cases are closely related to a pair of first-half cousins in the past, indicating a familial disease. In addition, genetics contributed more to the thyroid follicular cell carcinoma than other factors by an estimated heritability of 0.62 based on pedigree. The age of diagnosis ranged between 4.5 and 13.5 years, and 76% of cases were diagnosed before 10 years of age, implying an early onset of disease. We observed a significant higher pedigree-based inbreeding coefficient in the affected dogs (mean F 0.23) compared to unaffected dogs (mean F 0.14), suggesting the contribution of inbreeding to tumour development. The unique occurrence of familial thyroid follicular cell carcinoma in this dog population and the large number of affected dogs make this population an important model to identify the genetic basis of familial thyroid follicular cell carcinoma in this breed and may contribute to the research into pathogenesis, prevention and treatment in humans.

Deleterious Mutations in the TPO Gene Associated with Familial Thyroid Follicular Cell Carcinoma in Dutch German Longhaired Pointers

“…The GLPs were highly inbred with a mean inbreeding coefficient estimated based on difference between observed and expected homozygotes of 0.50. Inbreeding was higher in affected (0.51) than in unaffected dogs (0.48) (Welch two sample test: p -value of 0.002) ( Figure 1 a), which is in agreement with our previous analysis based on inbreeding coefficients estimated from the pedigree [ 27 ]. In the genotyped affected dogs, 72% were male (18 out of 25), and in the unaffected dogs, this was 38% (10 out of 26).…”

“…As reported earlier [27], the FCC in these Dutch GLPs is a heritable disease and very likely a recessive trait. Most affected dogs are closely related.…”

“…All the German longhaired pointers used in this research were from the dataset described previously [ 27 ]. Briefly, in total, 264 GLPs were examined, and 84 cases were identified, of which 54 were histopathologically confirmed FCC cases, 1 was a follicular adenoma case, and 29 were suspected of thyroid neoplasia based on typical clinical signs such as the presence of cervical mass, but no further diagnostics were performed.…”

“…The histology assessments were performed by the Department of Pathology, Utrecht University. Detailed description of samples and diagnosis procedures can be found in the previous study [ 27 ].…”

“…Previously, we reported a large number of familial FCC in the Dutch German longhaired pointers (GLPs). The pedigree suggests a recessive mode of inheritance [ 27 ]. The aim of the current study was to identify the germline causal gene(s) of familial FCC in the GLP population.…”