Comparative oncology · reverse-lookup · candidate
Insulinoma
Human insulinoma has known somatic drivers. No one has sequenced the canine tumors. So this asks the honest reverse question: dogs carry the ortholog of each human driver, which makes them candidate models, and the fact that no canine tumor has been characterized is itself the finding worth naming.
No canine insulinoma tumor has ever been sequenced for somatic drivers. The published canine literature is transcriptomic and clinical only (Capodanno 2020 RNA-seq n=9; Capodanno 2022 review). So whether the human insulinoma drivers below also drive the canine disease is UNKNOWN. This is a candidate model and a documented gap, not a canine finding.
Human driver, dog ortholog, canine status
Each human driver of insulinoma (cohort-cited), the dog ortholog we hold for it, and the honest canine status. A candidate is not a verdict: the dog carrying the gene is not the dog getting the mutation.
THE human insulinoma driver: 25% (21/84, Hong 2020), insulinoma-specific (0/127 non-functional pNET). Dogs carry a one2one YY1 ortholog at 98.3% protein identity, but YY1/T372R has NEVER been assessed in canine insulinoma. This is the single largest translational-genomic gap for the canine model.
Low in human insulinoma (~2%) unlike non-functional pNET (42 to 45%), the key human distinction; Capodanno 2022 states MEN1 is qualitatively not involved in canine insulinoma either. Dog ortholog held (one2one, 96.4% identity). Canine tumor status otherwise unsequenced.
The mTOR pathway is altered in a subset of pancreatic neuroendocrine tumors; the insulinoma-specific PTEN frequency is not separately tabulated, so it abstains. Capodanno 2020 saw the PI3K pathway upregulated in canine insulinoma metastases at the EXPRESSION level only (RNA-seq, not a somatic mutation). Dog ortholog held at 100% identity; the human gene carries germline ClinVar disease evidence.
A PI3K-pathway node relevant to the mTOR axis in pancreatic neuroendocrine tumors; insulinoma-specific frequency abstains. Dog ortholog held (one2one, 99.8% identity). PIK3CA is a shared driver in other canine cancers (mammary, hemangiosarcoma), which is exactly the kind of cross-cancer link this bridge makes visible.