Molecular characterization of canine follicular and medullary thyroid carcinomas

Background: Thyroid tumors represent 1–3% of canine cancers with most classified as follicular carcinomas. Medullary carcinomas arising from c-cells are less frequently diagnosed in both dogs and humans. In comparison, papillary thyroid the common type human cancer (70–80%) 10–15% cases. 2% cases 20% these associated inherited gene mutations RET. Human bear activating BRAF NRAS. Materials Methods: To determine if share molecular characteristics, we conducted whole exome (WES) RNA sequence analysis tumors. We used capture (Agilent Sure Select V2) to 27 matched normal genomic samples ribosomal depleted total was sequenced 30 The were histologically typed solid, compact, or follicular, adenocarcinomas, contained >70% tumor tissue. Results: For WES, 150 bp paired end reads (Illumina) mapped against CanFam3.1 using BWA short variants called annotated Mutect2 VEP tools. Average depth sequencing 212 ± 27. RNAseq STAR normalized counts generated DESeq2. Protein coding somatic per ranged 17 346 (total 2181). Known genes 2 more SALL4, HSP90AA1, MEN1, SFPQ, LEPROTL1, CDK4, RAD17, MGAM, NOTCH4, RANBP2. No identified NRAS, although individual unknown impact KRAS, ARAF, RASA1. Individual also had TSHR THRAP3. Hierarchical clustering expression data separated into groups: C1 C2. Differential between groups high (>1000-fold change) calcitonin transcripts C1, suggesting that cluster is comprised medullary Notable among upregulated relative C2 were: FOXA1, SCG5, RET, ERBB4, NTRK1, WNK2, MUC1. Upregulated included: FGFR2, MECOM, PAX8, ERBB2, GRM3, AR, SMO, IGF2BP2, SOCS1. Pre-ranked set enrichment (GSEA) “Hallmark KRAS signaling UP” “GOBP Regulation Membrane Potential” pathways enriched while for limited, hormone generation” being significant. Conclusions: These suggest dog, like their counterparts, may be driven by RET signaling. contrast, show limited reliance on RAS/RAF oncogenic progression. conflict interest.