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Published on: May 16, 2020
Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants
Leire Torices1, Caroline E Nunes-Xavier1,2, José I López1
1Biobizkaia Health Research Institute, Barakaldo, Spain.
Abstract:
PTEN is a major tumor suppressor gene frequently mutated in human tumors, and germline PTEN gene mutations are the molecular diagnostic of PTEN Hamartoma Tumor Syndrome (PHTS), a heterogeneous disorder that manifests with multiple hamartomas, cancer predisposition, and neurodevelopmental alterations. A diversity of translational and splicing PTEN isoforms exist, as well as PTEN C-terminal truncated variants generated by disease-associated nonsense mutations. However, most of the available anti-PTEN monoclonal antibodies (mAb) recognize epitopes at the PTEN C-terminal tail, which may introduce a bias in the analysis of the expression of PTEN isoforms and variants. We here describe the generation and precise characterization of anti-PTEN mAb recognizing the PTEN C2-domain, and their use to monitor the expression and function of PTEN isoforms and PTEN missense and nonsense mutations associated to disease. These anti-PTEN C2 domain mAb are suitable to study the pathogenicity of PTEN C-terminal truncations that retain stability and function but have lost the PTEN C-terminal epitopes. The use of well-defined anti-PTEN mAb recognizing distinct PTEN regions, as the ones here described, will help to understand the deleterious effects of specific PTEN mutations in human disease.
Insights
New antibodies targeting the PTEN C2-domain can detect PTEN variants missed by current methods. This advancement aids in understanding PTEN gene mutations in PTEN Hamartoma Tumor Syndrome (PHTS) and cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- PTEN is a critical tumor suppressor gene frequently altered in human cancers.
- Germline PTEN mutations define PTEN Hamartoma Tumor Syndrome (PHTS), a disorder linked to hamartomas, cancer predisposition, and developmental issues.
- Existing anti-PTEN antibodies often target the C-terminal tail, potentially biasing the analysis of PTEN isoforms and disease-associated variants.
Purpose of the Study:
- To generate and characterize novel monoclonal antibodies (mAbs) against the PTEN C2-domain.
- To utilize these new mAbs for monitoring PTEN expression, including isoforms and C-terminal truncations.
- To investigate the functional impact of PTEN mutations in disease.
Main Methods:
- Generation and precise characterization of anti-PTEN C2-domain monoclonal antibodies.
- Application of these antibodies to analyze PTEN expression and function.
- Assessment of PTEN variants, including missense and nonsense mutations.
Main Results:
- Successfully generated and characterized anti-PTEN mAbs targeting the C2-domain.
- These novel antibodies can detect PTEN isoforms and C-terminal truncated variants, including those missed by C-terminal-specific antibodies.
- Demonstrated the utility of C2-domain mAbs in studying PTEN mutations associated with disease.
Conclusions:
- Novel anti-PTEN C2-domain mAbs provide a valuable tool for comprehensive PTEN analysis.
- These antibodies overcome limitations of existing reagents, enabling better study of PTEN variants and their role in PHTS and cancer.
- Facilitates a deeper understanding of the pathogenic mechanisms of PTEN mutations in human diseases.
