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Expression of the tumor suppressor genes NF2, 4.1B, and TSLC1 in canine meningiomas
P J Dickinson1, E I Surace, M Cambell
1Department of Surgical and Radiological Sciences, Tupper Hall, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA. pjdickinson@ucdavis.edu
Abstract:
Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) (NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.
Insights
Canine meningiomas frequently show reduced expression of tumor suppressor genes like 4.1B and TSLC1, suggesting their role in tumor development. Other unidentified genes may also contribute to canine brain tumor formation.
Area of Science:
- Veterinary oncology
- Molecular genetics
- Canine brain tumors
Background:
- Meningiomas are common primary brain tumors in dogs.
- The molecular mechanisms driving canine meningioma development are poorly understood.
- Human meningioma pathogenesis involves tumor suppressor genes like NF2, 4.1B, and TSLC1.
Purpose of the Study:
- To investigate the expression of NF2, 4.1B, and TSLC1 tumor suppressor genes in spontaneous canine meningiomas.
- To determine if alterations in these genes correlate with tumor characteristics.
- To understand the potential role of these genes in canine meningioma tumorigenesis.
Main Methods:
- Quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) for NF2 gene expression (n=25).
- Western blotting for NF2/merlin, 4.1B, and TSLC1 protein expression (n=30).
- Analysis of gene expression data in relation to tumor grade, subtype, and location.
Main Results:
- Decreased expression of 4.1B and TSLC1 proteins was observed in 20% and 50% of tumors, respectively.
- 60% of meningiomas showed reduced or absent expression of either 4.1B or TSLC1.
- NF2 gene expression varied, with no complete loss of protein, unlike 4.1B and TSLC1. TSLC1 abnormalities mirrored human meningiomas; NF2 and 4.1B perturbations were less common than in humans.
- No significant association was found between tumor suppressor gene expression and tumor grade, subtype, or location.
Conclusions:
- Loss of 4.1B and TSLC1 tumor suppressor gene expression is frequent in canine meningiomas.
- These genetic alterations may represent early events in canine meningioma tumorigenesis.
- Other unidentified genes likely play a significant role in the formation and growth of canine meningiomas.
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