Ultra-frequent HRAS p.Q61R somatic mutation in canine acanthomatous ameloblastoma reveals pathogenic similarities with human ameloblastoma

摘要: Ameloblastoma is a locally aggressive odontogenic tumour that occurs in humans and dogs. Most ameloblastomas (AM) harbour mutually-exclusive driving mutations BRAF, HRAS, KRAS, NRAS or FGFR2 activate MAPK signalling, SMO activates Hedgehog signalling. The remarkable clinical histological similarities between canine acanthomatous ameloblastoma (CAA) AM suggest they may similar mutations. In this study, aimed at characterizing the mutational status of SMO, CAA, we used RNA sequencing, Sanger sequencing restriction fragment length polymorphism assays to demonstrate 94% CAA (n = 16) somatic HRAS p.Q61R mutation. MAPK-activating profiles implicate conserved molecular mechanisms tumorigenesis, thus, qualifying dog as potentially useful model disease. Given relevance RAS pathogenesis tumours other types cancer, results study are comparative, translational, veterinary value.