Comparative oncology / research surface

Lymphoma: the dog as a natural model of human B-cell lymphoma.

Canine B-cell lymphoma, especially diffuse large B-cell lymphoma, is one of the most-studied natural models of human DLBCL. The canine driver landscape is unusually well characterized across five cohorts, and it shares its core with the human disease.

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 · 2 genes

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

TP53

tumor suppressor; a shared driver of both diseases

Dog

14%

of 86 tumors · SNV

Human

25%

of 574 tumors · mutation

TRAF3

NF-kB pathway regulator; the flagship conserved driver

Dog

45%

of 86 tumors · inactivating SNV/indel

Human

—

not encoded (see note)

The flagship canine-model finding: TRAF3 is somatically inactivated in ~45% of canine B-cell lymphoma versus ~9% (locus loss) in human DLBCL (Blood 2015) -- the dog dramatically amplifies a conserved, human-relevant NF-kB driver.

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.

FBXW7 · Dog-side

20% of 86

ubiquitin-ligase tumor suppressor · SNV

Its recurrent codon is shared across human cancers, but FBXW7 is not a recurrent human-DLBCL driver -- canine-enriched.

POT1 · Dog-side

15% of 86

shelterin / telomere-protection · SNV

A germline predisposition gene in humans, not a recurrent somatic DLBCL driver -- a canine-enriched somatic event.

DDX3X · Dog-side

20% of 86

RNA helicase · SNV

Recurrent in human Burkitt lymphoma; lower in DLBCL, so not encoded on the human side here.

SETD2 · Dog-side

13% of 86

histone H3K36 methyltransferase · SNV

Present in human DLBCL at lower frequency; a shared chromatin-regulator pathway, exact human cohort % not extracted.

MYC · Dog-side

13% of 86

oncogene · SNV

In human DLBCL MYC acts predominantly through translocation / double-hit -- a different lesion class than the canine point mutations, so not encoded as a comparable human cell.

The human landscape

Beyond the shared core, human DLBCL is classified by drivers the canine cohorts do not carry prominently: KMT2D (~25%), the MYD88 / CD79B axis (the MCD/ABC subtype), EZH2 (~6% overall, ~22% in GCB), and CREBBP (~11%). Exact per-cohort frequencies live in Schmitz 2018 and the Bakhshi 2020 review; we cite them here rather than restate a number we could not extract from the primary table.