ESEBEC2016 Oral Communications (1) (8 abstracts)
TERT promoter mutations in pancreatic endocrine tumours are frequent in tumours from patients with hereditary syndromes
João Vinagre 1, , Joana Nabais 4 , Jorge Pinheiro 5 , Rui Batista 1, , Rui Oliveira 6 , Pedro Gonçalves 1, , Ana Pestana 1, , Marta Reis 1, , Bárbara Mesquita 1, , Vasco Pinto 1, , Joana Lyra 1, , Miguel Godinho 4 , José Manuel Lopes 1, , Manuel Sobrinho-Simões 1, & Paula Soares 1,
1i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal; 2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-465 Porto, Portugal; 3Institute of Biomedical Sciences of Abel Salazar, University of Porto, 4050-313 Porto, Portugal; 4Instituto Gulbenkian de Ciência (IGC), 2780-156 Oeiras, Portugal; 5Department of Pathology, Centro Hospitalar de S. João, 4200-319 Porto, Portugal; 6Department of Pathology, Centro Hospitalar de Coimbra, 3041-801 Coimbra, Portugal; 7Medical Faculty of the University of Porto, 4200-319 Porto, Portugal.
Objective: One of the hallmarks of cancer is its unlimited replicative potential. Recently, telomerase promoter (TERTp) mutations were presented as novel mechanism for telomerase re-activation/expression. Due to this fact, it was our objective to study pancreatic endocrine tumours (PET) and related cell lines, to determine if TERTp mutations were present.
Design: We performed characterization of the TERTp in a series of 55 PETs and three common PET cell lines. TERTp mutations were evaluated if they could represent an alternative mechanism in PETs. Additionally, we tested functionally the mutations in vitro, and performed chromatin immunoprecipitation to determine what were the fundamental transcription factors acting on the novel binding sites generated by the mutations.
Results: TERTp mutations were detected in 7% of the cases studied and were mainly associated to patients harbouring hereditary syndromes. In vitro, these mutations confer a two to fourfold increase in telomerase transcription activity. They are able to recruit ETS transcription factor members, in particular GABP-α and ETV1. The findings obtained in tumours are also recapitulated in the cell lines, where TERTp mutated cell line does not rely on alternative lengthening of telomeres mechanism.
Conclusions: We report for the first time TERTp mutations in PETs and derived cell lines. In our series, the mutations were noticeably prevalence in cases with a hereditary component. The data we present point these mutations as an alternative mechanism and in an exclusive manner. In vitro, these alterations are functional and perform in the same manner as presented in other cancer models.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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