Comparative oncology / research surface

Mammary carcinoma: the dog as a natural model of human disease.

Naturally-occurring canine mammary carcinoma is a clinically similar model of human breast cancer, and here the driver genetics line up too: the PIK3CA H1047R hotspot, one of the defining driver mutations of human breast cancer, is the single most common mutation in canine mammary tumors. Below is the canine somatically-altered driver, cited, with that shared hotspot 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 →

The conserved core

concordant · 1 genes

Drivers where dog and human agree on status for this comparable cancer (commensurability-gated). That agreement is the evidence the dog models the human disease here.

PIK3CA concordant

oncogene; PI3K catalytic subunit. The H1047R (A3140G) hotspot is the SAME driver-mutation hotspot in canine mammary tumors and human breast cancer - the cleanest matched-driver case in this comparison. Overall, PIK3CA is the most frequently mutated gene in canine mammary tumors (45%, 9/20 WES)

Dog

29%

of 62 tumors · H1047R (A3140G) hotspot mutation

Lee et al. 2019

Human

—

rate not tabled (see basis)

Human basis: 14.3% at the SAME H1047R hotspot in human breast cancer (Lee 2019).

The SAME PIK3CA H1047R hotspot defines human breast cancer, where it occurs in 14.3% (cited in Lee 2019); the canine rate (29%) is higher, and the hotspot itself is shared. The human comparison is kept in prose rather than tabled because the source gives the human frequency without a cohort size (cite-or-abstain).

fused signature constraint LOEUF 0.221 ortholog dog↔human high-corroborated germline 5 ClinVar syndromes