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. 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 · 3 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.

TP53 concordant

tumor suppressor; the dominant osteosarcoma driver in both species

Dog

71%

of 24 tumors · point mutation

Gardner et al. 2019

Human

82%

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

Chen et al. 2014

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.

fused signature constraint LOEUF 0.449 ortholog dog↔human high-corroborated germline 11 ClinVar syndromes

RB1 concordant

tumor suppressor; RB cell-cycle pathway

Dog

29%

of 24 tumors · copy-number loss

Gardner et al. 2019

Human

61%

of 59 tumors · deletion

Perry et al. 2014

fused signature constraint LOEUF 0.239 ortholog dog↔human high-corroborated

PTEN concordant

tumor suppressor; PI3K/mTOR pathway

Dog

45%

of 24 tumors · copy-number loss

Gardner et al. 2019

Human

13.6%

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

Perry et al. 2014

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.

fused signature constraint LOEUF 0.685 ortholog dog↔human high germline 14 ClinVar syndromes

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.

ATRX divergent

chromatin remodeler; ALT telomere maintenance

Dog

—

see cited basis

Human

29%

of 34 tumors · mutation + focal deletion/SV

Chen et al. 2014

Dog (cited): not reported recurrently altered in the canine OS cohort (Gardner 2019)

Human (cited): 29% in human OS (Sakthikumar; full text paywalled but the rate is cited)

A human-side driver characterized as absent in the canine cohort; both sides characterized, they disagree (human direction).

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

Canine-enriched drivers

darkness · 3

Recurrent in the canine cohort; the human side is not established as a recurrent driver here or is unquantified. Coverage darkness, not a measured disagreement (INV-81 / INV-77).

SETD2 canine-enriched

42% of 24

histone H3K36 methyltransferase; epigenetic regulator · mutation + deletion + translocation · Gardner et al. 2019

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

DMD canine-enriched

50% of 24

dystrophin locus; recurrent structural-variant target in canine OS · copy-number loss + translocation · Gardner et al. 2019

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

MYC canine-enriched

38% of 24

oncogene; amplification · copy-number gain · Gardner et al. 2019

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