Comparative oncology / research surface

Mast cell tumor: the dog as a natural model of human disease.

Mast cell tumor is one of the most common skin cancers in dogs, and it is driven by the same gene that drives human mast cell disease, KIT. There is an honest twist worth stating plainly: dogs and people break KIT in different places. Below is the canine driver, cited, with that divergence made explicit. These are somatic tumor alterations reported as cohort frequencies, a portrait of the disease across dogs, never a germline carrier status and never an individual-dog prediction.

These are somatic tumor alterations, not a germline carrier status. Every number here is a cohort frequency, the fraction of sequenced tumors somatically altered in a gene, reported by a published study. It is not a variant a dog inherits or carries, and it is not a prediction about any individual dog. Cross-species labels (concordant, divergent, canine-enriched) come from a commensurability-gated concordance map (INV-81), not a coarse shared flag.

This is the molecular driver landscape for this cancer. all cancers →

Where dog and human diverge

divergent · 1

Both sides characterized for a commensurable lesion, and they disagree. The honest limit of the model, not darkness and not a missing rate filled with zero.

KIT divergent

receptor tyrosine kinase; the driver of canine mast cell tumor via juxtamembrane internal tandem duplications (exon 11 12.9%, exon 8 9.7%), which lock KIT on without its ligand. KIT drives human mast cell disease too, but through the kinase-domain D816V mutation, so the gene is shared while the lesion diverges

Dog

29%

of 62 tumors · KIT-activating mutation (juxtamembrane exon-8/11 internal tandem duplications; no kinase-domain mutations)

Montanucci et al. 2024

Human

—

see cited basis

Dog (cited): 29% exon-11 internal tandem duplication in canine MCT (Montanucci 2024)

Human (cited): human mastocytosis is defined by the kinase-domain exon-17 KIT D816V; canine MCT carries NO exon-17 mutation (Montanucci 2024)

Same gene, same cell lineage (mast cell), both activating, but a different exon/mechanism - the atom's explicit 'honest divergence'. Commensurable at the gene+lineage level. (Separately, canine GIST DOES match human GIST exon-11, a concordance in a different tumor type not scored here.)

The honest divergence: canine MCT carries NO exon-17 (kinase-domain) mutations, whereas human mastocytosis is defined by the kinase-domain KIT D816V. Separately, canine gastrointestinal stromal tumors (GISTs) DO share human GIST's KIT exon-11 mutations - a matched model in a different tumor type.

fused signature constraint LOEUF 0.24 ortholog high