Comparative oncology / research surface

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

Hemangiosarcoma is one of comparative oncology's most important natural models. Naturally-occurring canine hemangiosarcoma, studied here in golden retrievers, closely mirrors the genomic landscape of human angiosarcoma of the breast and viscera, both converging on the PI3K and MAPK pathways. Below is the shared somatically-altered driver landscape, drawn from a peer-reviewed golden-retriever cohort and cited to its source. 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 side. For how often these cancers strike goldens over a lifetime, see the Golden Retriever Lifetime Study cohort → · all cancers →

The conserved core

concordant · 2 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 hemangiosarcoma and angiosarcoma driver in both species

Dog

59.6%

of 47 tumors · somatic mutation

Megquier et al. 2019

Human

29%

of 30 tumors · somatic mutation

Megquier et al. 2019

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

PIK3CA concordant

oncogene; PI3K catalytic subunit -- the PI3K pathway that drives both diseases

Dog

29.8%

of 47 tumors · somatic mutation

Megquier et al. 2019

Human

20%

of 30 tumors · somatic mutation

Megquier et al. 2019

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

KDR divergent

VEGFR2 receptor tyrosine kinase; angiogenesis -- a hallmark HUMAN angiosarcoma driver

Dog

2.1%

of 47 tumors · somatic mutation (1 of 47 cases)

Megquier et al. 2019

Human

—

see cited basis

Dog (cited): 2.1% (1/47) in canine HSA (Megquier 2019)

Human (cited): >20% KDR (VEGFR2) alteration in human angiosarcoma (Megquier 2019)

The honest limit of the model, called out in the atom: both sides measured, human much higher than dog.

The honest limit of the model: KDR (VEGFR2) is altered in over 20% of human angiosarcomas but only 2.1% (1/47) of these canine HSAs. Where dog and human diverge, we say so -- the model is powerful, not identical.

fused signature constraint LOEUF 0.328 ortholog high-corroborated

Canine-enriched drivers

darkness · 4

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).

PIK3R1 canine-enriched

8.5% of 47

PI3K regulatory subunit; a second hit on the same PI3K axis as PIK3CA · somatic mutation · Megquier et al. 2019

Not separately quantified in the compared human angiosarcoma cohort -- reinforces the PI3K pathway on the canine side.

ORC1 canine-enriched

8.5% of 47

origin recognition complex subunit; DNA replication licensing · somatic mutation · Megquier et al. 2019

A recurrent canine HSA driver (Megquier 2019); not reported recurrent in the compared human cohort.

RASA1 canine-enriched

8.5% of 47

RAS GTPase-activating protein; a negative regulator of the RAS/MAPK pathway, so loss activates MAPK · somatic mutation · Megquier et al. 2019

A recurrent canine HSA driver on the MAPK axis (Megquier 2019); the MAPK pathway is shared with human angiosarcoma even where the exact gene differs.

ARPC1A canine-enriched

6.4% of 47

actin-related protein 2/3 complex subunit; cytoskeletal regulator · somatic mutation · Megquier et al. 2019

A recurrent canine HSA driver (Megquier 2019); not reported recurrent in the compared human cohort.