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News Article

Canine melanoma study identifies genetic basis of disease


Canine malignant melanoma is a significant cause of mortality in dogs and an important comparative model for human melanoma

Researchers at the Translational Genomics Research Institute (TGen), based in Arizona, USA, together with collaborators, have used multiple genomic analysis techniques to identify several gene mutations that could be the keys to what drives melanoma in dogs.

The researchers specifically identified mutations in PTPRJ, a tumor suppressor gene; the findings are published in the journal PLOS Genetics.

“This mutational landscape of canine melanoma resembles that seen in human melanoma subtypes found in sun-shaded areas of the body, such as the nose and mouth, which remain difficult to treat. This similarity means that we have a genetic bridge across which understanding of the disease in either species can inform the other,” said Dr. Will Hendricks, a TGen Assistant Professor of Integrated Cancer Genomics, and the study’s lead author.

While melanoma is commonly associated with skin cancer, different types of melanoma can originate in different parts of the body, and it often spreads to the lungs, lymph nodes, bones and brain.

Researchers looked at 37 canine tumors and 17 control samples from a variety of dog breeds, and used several genomic analysis tools, including: whole genome sequencing, RNA sequencing, array comparative genomic hybridization, single nucleotide polymorphism array, and targeted Sanger sequencing analyses.

“Malignant melanoma is a significant cause of death among domestic dogs, and also provides a powerful comparative model for melanoma among humans,” said Dr. Jeffrey Trent, TGen President and Research Director, and the study’s senior author. “Overall, these data inform biological comparisons between canine and human melanoma, while suggesting actionable targets for both."

The study found mutations in the PTPRJ gene in seven of the tumors, and cancer-activating mutations in the RAS gene in nine of the tumors, in addition to changes in the genes MDM2 and TP53.

“Our genetic understanding of canine melanoma now allows us to continue to work to understand melanoma biology, and serves as a roadmap to developing and evaluating new treatment strategies,” Dr. Hendricks said.

The study examined several dog breeds with a propensity for melanoma, including Cocker Spaniels, an English Cocker Spaniel and a Labrador retriever. The paper notes that an expanded study of breed-specific groups will be critical for further understanding of melanoma among dogs.

Also contributing to this study were: the National Cancer Institute (NCI); Mayo Clinic; Arizona State University; North Carolina State University; University of California, Davis; Colorado State University; University of Queensland; Van Andel Research Institute; Spectrum Health; Innogenics Inc.; and The Veterinary Cancer Center.

Read article: Somatic inactivating PTPRJ mutations and dysregulated pathways identified in canine malignant melanoma by integrated comparative genomic analysis by William P. D. Hendricks, Victoria Zismann, Karthigayini Sivaprakasam, Christophe Legendre, Kelsey Poorman, Waibhav Tembe, Nieves Perdigones, Jeffrey Kiefer, Winnie Liang, Valerie DeLuca, Mitchell Stark, Alison Ruhe, Roe Froman, Nicholas S. Duesbery, Megan Washington, Jessica Aldrich, Mark W. Neff, Matthew J. Huentelman, Nicholas Hayward, Kevin Brown, Douglas Thamm, Gerald Post, Chand Khanna, Barbara Davis, Matthew Breen, Alexander Sekulic and Jeffrey M. Trent published in PLOS Genetics (2018) 14(9): e1007589, doi: 10.1371/journal.pgen.1007589

Article details

  • Date
  • 11 September 2018
  • Source
  • TGen
  • Subject(s)
  • Dogs, Cats, and other Companion Animals