ERP131302 PRJEB47059 ena-STUDY-WAGENINGEN UNIVERSITY-18-08-2021-14:06:09:412-1227 Somatic mutation landscape of familial Follicular Cell Thyroid Carcinoma in dogs through high depth whole-genome sequencing Somatic mutation profile of thyroid cancer in dogs has not been investigated. We previously reported a familial thyroid follicular cell carcinoma (FCC) in a large number of Dutch German longhaired pointers and identified two deleterious mutations in the TPO gene associated with the disease predisposition. In this study, we comprehensively investigated the somatic mutations in the tumors that potentially contribute to the inherited tumor formation and development using high depth whole-genome sequencing. A GNAS A204D missense mutation was identified in 4 of 7 tumors by whole-genome sequencing and xx of 36 FCC tumors by PCR-RFLP. In humans, somatic mutations in the GNAS gene were also identified but in low prevalence. Meanwhile, the homologous mutation has not been reported. It suggested the potential interaction between germline risk factor and driver mutation by comparing to prevalence of GNAS mutations in human samples. Moreover, tumors with GNAS A204D mutation had significantly less somatic SNVs and Indels, suggesting that this mutation could be a marker for less malignant form of thyroid tumor in dogs. WGS of Canine Follicular Cell Thyroid Carcinoma Somatic mutation profile of thyroid cancer in dogs has not been investigated. We previously reported a familial thyroid follicular cell carcinoma (FCC) in a large number of Dutch German longhaired pointers and identified two deleterious mutations in the TPO gene associated with the disease predisposition. In this study, we comprehensively investigated the somatic mutations in the tumors that potentially contribute to the inherited tumor formation and development using high depth whole-genome sequencing. A GNAS A204D missense mutation was identified in 4 of 7 tumors by whole-genome sequencing and xx of 36 FCC tumors by PCR-RFLP. In humans, somatic mutations in the GNAS gene were also identified but in low prevalence. Meanwhile, the homologous mutation has not been reported. It suggested the potential interaction between germline risk factor and driver mutation by comparing to prevalence of GNAS mutations in human samples. Moreover, tumors with GNAS A204D mutation had significantly less somatic SNVs and Indels, suggesting that this mutation could be a marker for less malignant form of thyroid tumor in dogs. ENA-FIRST-PUBLIC 2022-09-25 ENA-LAST-UPDATE 2022-09-25