Comparative oncology / research surface

Osteosarcoma: the dog as a natural model of human disease.

Osteosarcoma is one of the clearest cases of comparative oncology: naturally-occurring canine OS is a conserved genetic model of human, especially pediatric, osteosarcoma. Both are driven by the same core tumor-suppressor losses. Below is the shared somatically-altered driver landscape, drawn from peer-reviewed cohorts and cited to each.

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. This surface reports where the biology is shared between the species, model-of, and abstains where a cohort did not report a gene.

This is the molecular side. For how often these cancers actually strike goldens over a lifetime, see the Golden Retriever Lifetime Study cohort → · all cancers →

The conserved core

shared · 3 genes

Driver genes somatically altered in the tumors of both species, the evidence that the dog models the human disease.

TP53

tumor suppressor; the dominant osteosarcoma driver in both species

Dog

71%

of 24 tumors · point mutation

Human

82%

of 34 tumors · intron-1 structural rearrangement + mutation + deletion

How to compare these
The two headline figures count different alteration types: the canine 71% is point mutations only (Gardner 2019), the human 82% includes structural rearrangements, mutations, and deletions (Chen 2014). Harmonized, they align closely: counting mutations plus copy-number alterations, canine TP53 is 83% (Sakthikumar 2018, N=66), matching the human 82%. TP53 in osteosarcoma is disrupted by structural rearrangements as much as by point mutations in both species.

RB1

tumor suppressor; RB cell-cycle pathway

Dog

29%

of 24 tumors · copy-number loss

Human

61%

of 59 tumors · deletion

PTEN

tumor suppressor; PI3K/mTOR pathway

Dog

45%

of 24 tumors · copy-number loss

Human

13.6%

of 59 tumors · deletion + mutation (8/59)

How to compare these
Not like-for-like: the canine 45% counts copy-number loss only (Gardner 2019); the human 13.6% counts deletions plus mutations (Perry 2014). The alteration sets differ, so the higher canine figure should not be read as PTEN being more disrupted in dogs, the cohorts counted different event types.

Where the cohorts differ

Reported as a recurrent driver in one species' cohort but not the other. An honest asymmetry, a genuine non-report shown as such, never filled with a zero.

SETD2 · Dog-side

42% of 24

histone H3K36 methyltransferase; epigenetic regulator · mutation + deletion + translocation

Not reported recurrently altered in the human pediatric OS cohorts (Chen 2014, Perry 2014) -- a canine-prominent driver.

DMD · Dog-side

50% of 24

dystrophin locus; recurrent structural-variant target in canine OS · copy-number loss + translocation

Not reported recurrently altered in the human OS cohorts (Chen/Perry) -- a canine-prominent driver.

MYC · Dog-side

38% of 24

oncogene; amplification · copy-number gain

Named within recurrent human-OS CNA pathways (Chen 2014) but not separately quantified -- left unencoded rather than guessed.

ATRX · Human-side

29% of 34

chromatin remodeler; ALT telomere maintenance · mutation + focal deletion/SV

Not reported recurrently altered in the canine OS cohort (Gardner 2019); the Sakthikumar full text is paywalled -- a human-side driver here.