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, Daniel Onofre Vidal

Research output: Contribution to journalArticlepeer-review

Abstract

Testicular germ cell tumors (TGCT) represent the second main cause of cancerrelated 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.

Original languageEnglish (US)
Pages (from-to)50608-50617
Number of pages10
JournalOncotarget
Volume8
Issue number31
DOIs
StatePublished - Feb 7 2017

Keywords

  • Biomarkers
  • DNA methylation
  • Prognosis
  • Refractory disease
  • Testicular germ cell tumor

ASJC Scopus subject areas

  • Oncology

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