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

Abstract

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 (<i>VGF, MGMT, ADAMTS1</i>, <i>CALCA</i>, <i>HOXA9, CDKN2B, CDO1</i> and <i>NANOG</i>) was evaluated in 72 primary TGCT by quantitative methylation specific PCR. A high frequency of <i>MGMT</i> (90.9%, 20/22; p=0.019) and <i>CALCA</i> (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 <i>MGMT</i> and 51.3% vs 77.0%; p=0.029 for <i>CALCA</i>). The findings of this study indicate that methylation of <i>MGMT</i> and <i>CALCA</i> are frequent and could be used as new molecular markers of prognosis in TGCT.