To explore if MGMT promoter methylation changes have a role in cisplatin chemoresistance, first we study its methylation status in cisplatin sensitive and resistant paired human non-seminomatous germ cancer cell lines. Secondly in xenograft paired tumors and after in human non-seminomatous germ cell primary tumors, from patients treated with cisplatin based chemotherapy. In general we found that cisplatin sensitive samples are related with MGMT promoter hypermethylation associated with its loss of expression. Resistance is present when MGMT promoter is not methylated and expressed. Clinically, the presence of MGMT promoter methylation is related with better overall survival (p = 0.025) in patients with testicular germ cell cancer. Inhibition of MGMT with O6-benzylguanine in vitro or in vivo increases the sensitivity to cisplatin and temozolomide, being this a possible chemotherapeutic approach to re-sensibilize human non-seminomatous germ cell refractory tumors.
Citation Format: Cátia Moutinho, Xavier Garcia-del-Muro, Elisabet Guino, August Vidal, Sara Puertas, Clara Muñoz, Josep Piulats, Alberto Villanueva, Manel Esteller. Loss of MGMT promoter methylation and resistance to cisplatin in non-seminomatous germ cell tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 432.
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