Parallels in human, dog oral tumors could speed new therapies

Date:
November 29, 2021
Source:
Cornell University
Summary:
Recent research compared the genetic expression profiles of a
nonlethal canine tumor and the rare, devastating human oral tumor
it resembles, laying the groundwork for potential translational
medicine down the road.



FULL STORY ========================================================================== Recent Cornell research compared the genetic expression profiles of a
nonlethal canine tumor and the rare, devastating human oral tumor it
resembles, laying the groundwork for potential translational medicine
down the road.


========================================================================== While canine acanthomatous ameloblastoma (CAA) is common and nonlethal, it
has a strong resemblance to an oral tumor in humans known as ameloblastoma (AM).

As a boarded veterinary dentist and oral surgeon, Dr. Santiago Peralta, associate professor at the College of Veterinary Medicine (CVM) and first author of the recent study in Scientific Reports, sees CAA in his clinic
all the time.

"This research was a good example of a full cycle of translational
research," Peralta said. "We took something we were dealing with
in the clinical setting, studied it in the bench setting and are now
hoping to use it to help veterinary patients and, potentially, humans."
The resemblance between CAA and AM had long been noted by scientists
and clinicians, but no one had confirmed any molecular similarities. A
previous study on AM tumors revealed the underlying mutations, piquing
the interest of Peralta and his CVM colleagues. "We wondered if we should
look at these mutations and see if they precipitate the canine tumor,"
Peralta said.

They did just that, publishing a study in Veterinary and Comparative
Oncology in 2019, that revealed that both AM and CAA shared mutations
in a well-known signaling pathway, known as the RAS-RAF-MAPK pathway.

In their most recent study, Peralta and his colleagues analyzed a large
genomic dataset generated by the Cornell Transcriptional Regulation
and Expression Facility (TREx) to better understand the biological
consequences of these mutations. While doing so, they compared the CAA
tumors with another common canine tumor (oral squamous cell carcinoma)
and healthy gum tissue. These samples were stored and made available
through the Cornell Veterinary Biobank and gene expression was profiled
with RNA sequencing by Dr. Jen Grenier and her team at TREx.

The team also used genomic data from human tissues to run comparisons,
thanks to their collaboration with a human oral cancer expert at the
University of Turku in Finland. Through analyzing these different
tissues, Peralta and his team were able to see that the mutations they
had identified in their earlier study were largely responsible for the
tumors they were seeing.

They also found that CAA and AM are very similar at a molecular level, reinforcing the notion that dogs represent a potentially useful natural
model of the human tumor. "All the dysregulated molecules and pathways
in CAA tumor tissues were consistent with the mutations we'd found and remarkably similar to those observed in AM," he said.

Now that they've connected the dots between the underlying mutations and dysregulated molecular pathways driving tumor formation, Peralta and his colleagues have been working to establish in vitro and in vivo models of different canine oral tumors that can be used to test potential drugs. Any drugs that might prove effective in treating oral tumors in dogs could
also be promising candidates for human patients with analogue disease.

"If dogs truly represent a useful clinical model of the disease, they
also represent an immense opportunity," Peralta said. Because the CAA
tumors are much more common in dogs than AM are in humans, scientists can rapidly enroll many more dogs in clinical trials and get more translatable
data from those trials.

Furthermore, dogs, which live in same type of environments as humans,
are more accurate models of disease than other animal models. "My goal
as a veterinarian is to bring solutions back to the clinic. We're not
there yet, but we've made a major step toward that," Peralta said.

========================================================================== Story Source: Materials provided by Cornell_University. Original written
by Lauren Cahoon Roberts. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Santiago Peralta, Gerald E. Duhamel, William P. Katt, Kristiina
Heikinheimo, Andrew D. Miller, Faraz Ahmed, Angela
L. McCleary-Wheeler, Jennifer K. Grenier. Comparative
transcriptional profiling of canine acanthomatous ameloblastoma
and homology with human ameloblastoma.

Scientific Reports, 2021; 11 (1) DOI: 10.1038/s41598-021-97430-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211129122821.htm

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