Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants

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.

Automated summary

PTEN is a tumor suppressor gene frequently mutated in human tumors, and its mutations are the diagnostic marker for PTEN Hamartoma Tumor Syndrome (PHTS), a disorder characterized by multiple hamartomas, cancer predisposition, and neurodevelopmental alterations. This study generated and characterized anti-PTEN monoclonal antibodies recognizing the PTEN C2-domain, which can be used to study the expression and function of PTEN isoforms and mutations associated with disease. These antibodies are suitable for investigating the pathogenicity of PTEN C-terminal truncations that have lost the PTEN C-terminal epitopes but retain stability and function.