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Tumor Biology

, Volume 37, Issue 4, pp 4901–4907 | Cite as

Hotspot TERT promoter mutations are rare events in testicular germ cell tumors

  • Flavio Mavignier Cárcano
  • Daniel Onofre Vidal
  • André van Helvoort Lengert
  • Cristovam Scapulatempo Neto
  • Luisa Queiroz
  • Herlander Marques
  • Fátima Baltazar
  • Camila Maria da Silva Martinelli
  • Paula Soares
  • Eduardo Caetano Albino da Silva
  • Luiz Fernando Lopes
  • Rui Manuel Reis
Original Article

Abstract

The abnormal activation of telomerase, codified by the telomerase reverse transcriptase (TERT) gene, is related to one of cancer hallmarks. Hotspot somatic mutations in the promoter region of TERT, specifically the c.-124:C>T and c.-146:C>T, were recently identified in a range of human cancers and have been associated with a more aggressive behavior. Testicular germ cell tumors frequently exhibit a good prognosis; however, the development of refractory disease is still a clinical challenge. In this study, we aim to evaluate for the first time the presence of the hotspot telomerase reverse transcriptase gene promoter mutations in testicular germ cell tumors. A series of 150 testicular germ cell tumor cases and four germ cell tumor cell lines were evaluated by PCR followed by direct Sanger sequencing and correlated with patient’s clinical pathological features. Additionally, we genotyped the telomerase reverse transcriptase gene promoter single nucleotide polymorphism rs2853669 (T>C) located at −245 position. We observed the presence of the TERT promoter mutation in four patients, one exhibited the c.-124:C>T and three the c.-146:C>T. No association between TERT mutation status and clinicopathological features could be identified. The analysis of the rs2853669 showed that variant C was present in 22.8 % of the cases. In conclusion, we showed for the first time that TERT promoter mutations occur in a small subset (~3 %) of testicular germ cell tumors.

Keywords

Testicular neoplasms Neoplasms, germ cell, and embryonal TERT protein Mutation Polymorphism, single nucleotide 

Notes

Acknowledgments

The authors acknowledge the support of the Center for Research Support (NAP), Barretos Cancer Hospital, Pio XII Foundation.

Compliance with ethical standards

Funding

This work was supported by the Barretos Cancer Hospital internal research funds (PAIP): Project “Microenvironment, metabolism and cancer” that was partially supported by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN), and through the Fundo Europeu de Desenvolvimento Regional (FEDER). R.M.R. has a National Counsel of Technological and Scientific Development (CNPq) scholarship.

Conflicts of interest

None

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (register number CAAE 12297713.0.0000.5437) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Flavio Mavignier Cárcano
    • 1
    • 2
  • Daniel Onofre Vidal
    • 3
    • 4
  • André van Helvoort Lengert
    • 3
    • 4
  • Cristovam Scapulatempo Neto
    • 3
    • 5
  • Luisa Queiroz
    • 6
  • Herlander Marques
    • 6
  • Fátima Baltazar
    • 7
    • 8
  • Camila Maria da Silva Martinelli
    • 3
  • Paula Soares
    • 9
    • 10
    • 11
  • Eduardo Caetano Albino da Silva
    • 5
  • Luiz Fernando Lopes
    • 3
    • 4
  • Rui Manuel Reis
    • 3
    • 7
    • 8
  1. 1.Department of Clinical OncologyBarretos Cancer HospitalBarretosBrazil
  2. 2.Barretos School of Health Sciences, Dr. Paulo Prata–FACISBBarretosBrazil
  3. 3.Molecular Oncology Research CenterBarretos Cancer HospitalBarretosBrazil
  4. 4.Barretos Children’s Cancer HospitalBarretosBrazil
  5. 5.Department of PathologyBarretos Cancer HospitalBarretosBrazil
  6. 6.Department of Medical OncologyHospital de BragaBragaPortugal
  7. 7.Life and Health Sciences Research Institute (ICVS), Health Sciences SchoolUniversity of MinhoBragaPortugal
  8. 8.ICVS/3B’s-PT Government Associate LaboratoryBraga/GuimarãesPortugal
  9. 9.Institute of Molecular Pathology and Immunology of the University of Porto–IPATIMUPPortoPortugal
  10. 10.Instituto de Investigação e Inovação em SaúdeUniversidade do PortoPortoPortugal
  11. 11.Medical FacultyUniversity of PortoPortoPortugal

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