title: Hotspot TERT promoter mutations are rare events in testicular germ cell tumors.
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.
authors.affiliation: Department of Clinical Oncology, Barretos Cancer Hospital, Barretos, Brazil.|Barretos School of Health Sciences, Dr. Paulo Prata-FACISB, Barretos, Brazil.
authors.forename: Flavio Mavignier
authors.initials: FM
authors.lastname: Cárcano
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, 1331, Rua Antenor Duarte Villela St, CEP 14784 400, Barretos, Sao Paulo, Brazil.|Barretos Children's Cancer Hospital, 3025, Avenida João Baroni, Barretos, Brazil.
authors.forename: Daniel Onofre
authors.initials: DO
authors.lastname: Vidal
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, 1331, Rua Antenor Duarte Villela St, CEP 14784 400, Barretos, Sao Paulo, Brazil.|Barretos Children's Cancer Hospital, 3025, Avenida João Baroni, Barretos, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: van Helvoort Lengert
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, 1331, Rua Antenor Duarte Villela St, CEP 14784 400, Barretos, Sao Paulo, Brazil.|Department of Pathology, Barretos Cancer Hospital, Barretos, Brazil.
authors.forename: Cristovam Scapulatempo
authors.initials: CS
authors.lastname: Neto
authors.affiliation: Department of Medical Oncology, Hospital de Braga, Braga, Portugal.
authors.forename: Luisa
authors.initials: L
authors.lastname: Queiroz
authors.affiliation: Department of Medical Oncology, Hospital de Braga, Braga, Portugal.
authors.forename: Herlander
authors.initials: H
authors.lastname: Marques
authors.affiliation: Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, 1331, Rua Antenor Duarte Villela St, CEP 14784 400, Barretos, Sao Paulo, Brazil.
authors.forename: Camila Maria
authors.initials: CM
authors.lastname: da Silva Martinelli
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto-IPATIMUP, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|Medical Faculty, University of Porto, 4200-319, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.affiliation: Department of Pathology, Barretos Cancer Hospital, Barretos, Brazil.
authors.forename: Eduardo Caetano Albino
authors.initials: EC
authors.lastname: da Silva
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, 1331, Rua Antenor Duarte Villela St, CEP 14784 400, Barretos, Sao Paulo, Brazil. lf.lopes@yahoo.com.|Barretos Children's Cancer Hospital, 3025, Avenida João Baroni, Barretos, Brazil. lf.lopes@yahoo.com.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Lopes
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, 1331, Rua Antenor Duarte Villela St, CEP 14784 400, Barretos, Sao Paulo, Brazil. rreis@ecsaude.uminho.pt.|Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal. rreis@ecsaude.uminho.pt.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal. rreis@ecsaude.uminho.pt.
authors.forename: Rui Manuel
authors.initials: RM
authors.lastname: Reis
mesh_terms: D000328:Adult; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009373:Neoplasms, Germ Cell and Embryonal / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*; D013736:Testicular Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: Mutation; Neoplasms, germ cell, and embryonal; Polymorphism, single nucleotide; TERT protein; Testicular neoplasms