Research Papers:

MGMT and CALCA promoter methylation are associated with poor prognosis in testicular germ cell tumor patients

Camila Maria da Silva Martinelli, André van Helvoort Lengert, Flavio Mavignier Cárcano, Eduardo Caetano Albino Silva, Mariana Brait, Luiz Fernando Lopes _ and Daniel Onofre Vidal

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Oncotarget. 2017; 8:50608-50617. https://doi.org/10.18632/oncotarget.11167

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Camila Maria da Silva Martinelli1,7, André van Helvoort Lengert1,7, Flavio Mavignier Cárcano2,3,7, Eduardo Caetano Albino Silva4,7, Mariana Brait5, Luiz Fernando Lopes3,6,7 and Daniel Onofre Vidal1,6,7

1Pediatric Oncology Laboratory, Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil

2Department of Clinical Oncology, Barretos Cancer Hospital, Barretos, SP, Brazil

3Barretos School of Health Sciences, Dr. Paulo Prata/FACISB, Barretos, SP, Brazil

4Department of Pathology, Barretos Cancer Hospital, Barretos, SP, Brazil

5Department of Otolaryngology and Head & Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

6Barretos Children’s Cancer Hospital, Barretos, SP, Brazil

7Brazilian Childhood Germ Cell Tumor Study Group, Brazilian Pediatric Oncology Society, São Paulo, SP, Brazil

Correspondence to:

Luiz Fernando Lopes, email: [email protected]

Daniel Onofre Vidal, email: [email protected]

Keywords: DNA methylation, biomarkers, prognosis, refractory disease, testicular germ cell tumor

Received: January 25, 2016     Accepted: July 26, 2016     Published: August 10, 2016


Testicular germ cell tumors (TGCT) represent the second main cause of cancer-related death in young men. Despite high cure rates, refractory disease results in poor prognosis. Epigenetic reprogramming occurs during the development of seminomas and non-seminomas. Understanding the molecular and genetic basis of these tumors would represent an important advance in the search for new TGCT molecular markers. Hence the frequency of methylation of a gene panel (VGF, MGMT, ADAMTS1, CALCA, HOXA9, CDKN2B, CDO1 and NANOG) was evaluated in 72 primary TGCT by quantitative methylation specific PCR. A high frequency of MGMT (90.9%, 20/22; p=0.019) and CALCA (90.5%, 19/21; p<0.026) methylation was associated with non-seminomatous tumors while CALCA methylation was also associated with refractory disease (47.4%, 09/19; p=0.005). Moreover, promoter methylation of both genes predicts poor clinical outcome for TGCT patients (5-year EFS: 50.5% vs 77.1%; p=0.032 for MGMT and 51.3% vs 77.0%; p=0.029 for CALCA). The findings of this study indicate that methylation of MGMT and CALCA are frequent and could be used as new molecular markers of prognosis in TGCT.

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