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Updated: Dec 29, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Recurrent gene mutations detected in canine mast cell tumours by next generation sequencing
Miluse Vozdova1, Svatava Kubickova1, Karol Pal2
1Department of Genetics and Reproduction, Central European Institute of Technology, Veterinary Research Institute, Brno, Czech Republic.
Abstract:
Genetic causes of canine mast cell tumours (MCTs), except for mutations in the KIT gene detected in some MCTs, are generally unknown. We used whole exome sequencing to reveal mutation spectra in canine MCTs. We detected somatic mutations in 87 genes including 10 genes recognized as human cancer drivers. Besides KIT, 14 other genes were recurrently mutated. Subsequently, we performed next generation sequencing of a panel of 50 selected genes in additional MCT samples. In this group, the most frequently altered gene was GNB1 showing a recurrent dinucleotide substitution at position of Gly116 in 30% of the MCT samples (n = 6/20) and Ile80 substitution accompanied by a splice region mutation in one case. We extended the study by analysis of the above mentioned GNB1 regions in additional MCT samples by Sanger sequencing, and assessed the overall prevalence of GNB1 mutations to 17.3% (n = 14/81), which is similar to the prevalence of KIT alterations. Our results indicate that GNB1 mutations are probably involved in canine MCT pathogenesis in both cutaneous and subcutaneous MCT cases. As opposed to KIT alterations, the presence of GNB1 mutations did not negatively affect survival times, and our data even showed a trend towards positive prognosis. If our results are confirmed in a larger number of MCTs, an extension of molecular testing of canine MCTs by GNB1 analysis would help to refine the molecular stratification of MCTs, and become useful for targeted treatment strategies.
Insights
Genetic mutations in the GNB1 gene are common in canine mast cell tumors (MCTs), similar to KIT gene mutations. GNB1 mutations may indicate a positive prognosis for dogs with MCTs.
Area of Science:
- Veterinary Oncology
- Canine Genetics
- Molecular Pathology
Background:
- Canine mast cell tumors (MCTs) are common and their genetic underpinnings, beyond KIT gene mutations, remain largely unknown.
- Understanding the genetic landscape of MCTs is crucial for accurate diagnosis and targeted therapies.
Purpose of the Study:
- To identify novel genetic mutations associated with canine mast cell tumors using whole exome sequencing.
- To investigate the prevalence and prognostic significance of GNB1 gene mutations in canine MCTs.
Main Methods:
- Whole exome sequencing was performed to analyze mutation spectra in canine MCTs.
- Next-generation sequencing and Sanger sequencing were used to identify and validate mutations in selected genes, particularly GNB1.
- Statistical analysis was employed to assess the prevalence and correlation with survival times.
Main Results:
- Somatic mutations were detected in 87 genes, including 10 known human cancer drivers.
- Recurrent mutations were identified in 14 genes besides KIT.
- GNB1 mutations were found in 17.3% of canine MCTs, with specific recurrent substitutions at Gly116 and Ile80.
- GNB1 mutations were not associated with negative survival outcomes and showed a trend towards a positive prognosis.
Conclusions:
- GNB1 mutations are likely involved in the pathogenesis of both cutaneous and subcutaneous canine MCTs.
- GNB1 mutation analysis could refine molecular stratification of MCTs and aid in developing targeted treatment strategies.
- Further validation in larger cohorts is recommended to confirm the prognostic value of GNB1 mutations.
