TY - JOUR
T1 - MGMT and CALCA promoter methylation are associated with poor prognosis in testicular germ cell tumor patients
AU - Martinelli, Camila Maria da Silva
AU - Lengert, André van Helvoort
AU - Cárcano, Flavio Mavignier
AU - Silva, Eduardo Caetano Albino
AU - Brait, Mariana
AU - Lopes, Luiz Fernando
AU - Vidal, Daniel Onofre
N1 - Publisher Copyright:
© Martinelli et al.
PY - 2017/2/7
Y1 - 2017/2/7
N2 - 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.
AB - 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.
KW - Biomarkers
KW - DNA methylation
KW - Prognosis
KW - Refractory disease
KW - Testicular germ cell tumor
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U2 - 10.18632/oncotarget.11167
DO - 10.18632/oncotarget.11167
M3 - Article
C2 - 28881587
AN - SCOPUS:85026635235
SN - 1949-2553
VL - 8
SP - 50608
EP - 50617
JO - Oncotarget
JF - Oncotarget
IS - 31
ER -