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Comparative oncology / research surface

Melanoma: the dog as a model of human mucosal disease.

Canine melanoma is predominantly oral and mucosal, not sun-driven, which makes it a natural model of human MUCOSAL melanoma, not the common cutaneous form. Both are non-BRAF, low-mutation, and copy-number-driven, and a single cross-species study sequenced both.

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 · 5 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.

NRAS concordant

RAS/MAPK oncogene; the clean shared driver
Dog
11%
of 65 tumors · SNV (Q61, G12)
Wong et al. 2019
Human
18%
of 67 tumors · SNV
Newell et al. 2019
fused signature constraint LOEUF 0.55 ortholog dog↔human high-corroborated germline 5 ClinVar syndromes

TP53 concordant

tumor suppressor
Dog
8%
of 65 tumors · SNV
Wong et al. 2019
Human
9%
of 67 tumors · SNV
Newell et al. 2019
fused signature constraint LOEUF 0.449 ortholog dog↔human high-corroborated germline 11 ClinVar syndromes

MDM2 concordant

p53-axis oncogene (amplification); the conserved copy-number driver
Dog
29%
of 37 tumors · focal amplification (35% within the mucosal subset; CDK4 co-amplified)
Hendricks et al. 2018
Human
—
rate not tabled (see basis)

Human basis: conserved copy-number driver; ~70% of human mucosal tumors carry CDK4/CCND1/CDKN2A-axis alterations (Newell 2019).

The conserved copy-number driver. Rather than a single MDM2 %, human mucosal melanoma carries a broader amplification axis: ~70% of tumors have CDK4 / CCND1 / CDKN2A-axis alterations (Newell 2019). Copy-number-driven biology, not a BRAF/MAPK one.

fused signature constraint LOEUF 0.325 ortholog dog↔human high-corroborated

PTPRJ concordant

receptor tyrosine phosphatase; tumor suppressor
Dog
19%
of 37 tumors · inactivating / truncating (23% within the mucosal subset)
Hendricks et al. 2018
Human
—
rate not tabled (see basis)

Human basis: driver shared across canine oral and human mucosal melanoma (Wong 2019); exact human fraction not extractable.

Wong 2019 identifies PTPRJ as a driver shared across canine oral and human mucosal melanoma; the exact human fraction was not extractable from the primary table, so the human cell abstains.

fused signature constraint LOEUF 1.043 ortholog dog↔human high-corroborated

BRAF concordant

MAPK oncogene; the integrity marker
Dog
3%
of 65 tumors · SNV (effectively negative)
Wong et al. 2019
Human
16%
of 67 tumors · SNV
Newell et al. 2019

The key integrity point: BRAF drives ~50% of human CUTANEOUS melanoma but only ~16% of mucosal and ~0 to 3% of canine oral melanoma. Both diseases here are non-BRAF and non-UV, which is exactly why canine oral melanoma models human mucosal, not cutaneous, melanoma.

fused signature constraint LOEUF 0.237 ortholog dog↔human high-corroborated germline 10 ClinVar syndromes

Where dog and human diverge

divergent · 3

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.

KIT divergent

receptor tyrosine kinase; a human therapeutic target
Dog
—
see cited basis
Human
15%
of 67 tumors · SNV + amplification
Newell et al. 2019

Dog (cited): 0% (Wong 2019), ~8% (Hendricks) in canine oral melanoma

Human (cited): 15% in human mucosal melanoma (a driver and drug target)

A genuine cross-species divergence, both sides measured, stated not papered over.

A human-mucosal-enriched driver and drug target, largely absent in canine oral melanoma (0% in Wong, ~8% in Hendricks) -- a genuine cross-species divergence, stated not papered over.

fused signature constraint LOEUF 0.24 ortholog high

SF3B1 divergent

splicing factor
Dog
—
see cited basis
Human
12%
of 67 tumors · SNV (R625 hotspot)
Newell et al. 2019

Dog (cited): absent in the canine cohorts (Wong 2019)

Human (cited): 12% human-mucosal-specific R625 splicing driver

A human-mucosal-specific splicing driver, absent in the dog; both sides characterized.

A human-mucosal-specific splicing driver (R625 hotspot), absent in the canine cohorts -- a divergence.

NF1 divergent

RAS GTPase-activating tumor suppressor
Dog
—
see cited basis
Human
16%
of 67 tumors · SNV / loss
Newell et al. 2019

Dog (cited): not a reported recurrent canine driver (Wong 2019)

Human (cited): 16% recurrent in human mucosal melanoma

Recurrent in human mucosal, not canine; both sides characterized in the compared cohorts.

Recurrent in human mucosal melanoma; not a reported recurrent canine driver.

The human landscape

The shared genome-biology signature is the real model-of evidence: both diseases are non-UV, low-mutation-burden (~2 to 3 mutations/Mb), and copy-number / structural-variant-driven, unlike sun-driven cutaneous melanoma (which is ~15 to 30+ mut/Mb and ~50% BRAF-driven). That is exactly why the honest human comparator is mucosal, not cutaneous, melanoma (Wong 2019).