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Sci Rep. 2016 Jul 14;6:29714. doi: 10.1038/srep29714.

TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes.

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Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, 4200-135, Portugal.
Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, 4200-465, Portugal.
Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313, Porto, Portugal.
Instituto Gulbenkian de Ciência (IGC), Oeiras, 2780-156, Portugal.
Departmento de Patologia, Centro Hospitalar de S. João, Porto, 4200-319, Portugal.
Departmento de Patologia, Centro Hospitalar de Coimbra, Coimbra, 3041-801, Portugal.
Faculdade de Medicina da Universidade do Porto, Porto, 4200-139, Portugal.


One of the hallmarks of cancer is its unlimited replicative potential that needs a compensatory mechanism for the consequential telomere erosion. Telomerase promoter (TERTp) mutations were recently reported as a novel mechanism for telomerase re-activation/expression in order to maintain telomere length. Pancreatic endocrine tumors (PETs) were so far recognized to rely mainly on the alternative lengthening of telomeres (ALT) mechanism. It was our objective to study if TERTp mutations were present in pancreatic endocrine tumors (PET) and could represent an alternative mechanism to ALT. TERTp mutations were detected in 7% of the cases studied and were mainly associated to patients harbouring hereditary syndromes. In vitro, using PET-derived cell lines and by luciferase reporter assay, these mutations confer a 2 to 4-fold increase in telomerase transcription activity. These novel alterations are able to recruit ETS transcription factor members, in particular GABP-α and ETV1, to the newly generated binding sites. We report for the first time TERTp mutations in PETs and PET-derived cell lines. Additionally, our data indicate that these mutations serve as an alternative mechanism and in an exclusive manner to ALT, in particular in patients with hereditary syndromes.

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