OMIA 002171-9615 : Ameloblastoma in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 190020 (gene)

Mendelian trait/disorder: unknown

Mode of inheritance: Somatic Mutation

Considered a defect: yes

Species-specific name: Canine acanthomatous ameloblastomas (CAA)

Molecular basis: Saffari et al 2019: "By whole-exome sequencing, we have now discovered recurrent HRAS and BRAF activating mutations, respectively, in 63% and 8% of CAA. ... Strikingly, 11 of the 20 (55%) CAA cases carried activating HRAS mutations (10 HRAS-Q61R and 1 HRAS-G13R), and 2 of the 20 (10%) carried activating BRAF mutations (BRAF-V595E, orthologous to the human BRAF-V600E driver mutation) ... . Notably, cell lines derived from CAA with HRAS mutation exhibit marked sensitivity to MAP kinase (MAPK) pathway inhibitors, which constrain cell proliferation and drive ameloblast differentiation."

Peralta et al. (2019) "aimed at characterizing the mutational status of SMO, BRAF, HRAS, KRAS, NRAS and FGFR2 in CAA, we used RNA sequencing, Sanger sequencing and restriction fragment length polymorphism assays to demonstrate that 94% of CAA (n = 16) harbour a somatic HRAS p.Q61R mutation."

IT IS IMPORTANT TO NOTE THAT THESE ARE UNDERSTOOD TO BE A SOMATIC MUTATIONS, WHICH MEANS THAT THE VARIANTS ARE NOT INHERITED AND WILL NOT BE PASSED ON TO OFFSPRING

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
HRAS Harvey rat sarcoma viral oncogene homolog Canis lupus familiaris 18 NC_051822.1 (26230043..26227144) HRAS Homologene, Ensembl, NCBI gene

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2019 Peralta, S., McCleary-Wheeler, A.L., Duhamel, G.E., Heikinheimo, K., Grenier, J.K. :
Ultra-frequent HRAS p.Q61R somatic mutation in canine acanthomatous ameloblastoma reveals pathogenic similarities with human ameloblastoma. Vet Comp Oncol :, 2019. Pubmed reference: 31041834. DOI: 10.1111/vco.12487.
Saffari, P.S., Vapniarsky, N., Pollack, A.S., Gong, X., Vennam, S., Pollack, A.J., Verstraete, F.J.M., West, R.B., Arzi, B., Pollack, J.R. :
Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer. Oncogenesis 8:11, 2019. Pubmed reference: 30741938. DOI: 10.1038/s41389-019-0119-1.

Edit History


  • Created by Frank Nicholas on 27 Feb 2019
  • Changed by Frank Nicholas on 27 Feb 2019
  • Changed by Imke Tammen2 on 25 Aug 2021
  • Changed by Imke Tammen2 on 03 Feb 2022