MGMT and CALCA promoter methylation are associated with poor prognosis in testicular germ cell tumor patients
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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
Luiz Fernando Lopes, email: firstname.lastname@example.org
Daniel Onofre Vidal, email: email@example.com
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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