Ortiz Gómez León Darío, Contreras Martínez Heidy Johanna, Galvis Pareja David Andrés, Vélez Gómez Sara, Salazar Flórez Jorge Emilio, Monroy Fernando P, Peláez Sánchez Ronald Guillermo
Doctoral Program in Health Sciences, Graduate School, CES University, Medellín 050021, Colombia.
Cancer Institute, Las Americas-AUNA Clinic, Medellín 050023, Colombia.
Biomedicines. 2024 Dec 6;12(12):2777. doi: 10.3390/biomedicines12122777.
The treatment for patients with high-grade gliomas includes surgical resection of tumor, radiotherapy, and temozolomide chemotherapy. However, some patients do not respond to temozolomide due to a methylation reversal mechanism by the enzyme O-methylguanine-DNA-methyltransferase (MGMT). In patients receiving treatment with temozolomide, this biomarker has been used as a prognostic factor. However, not all patients respond in the same way, which suggests the existence of other proteins involved in resistance to temozolomide chemotherapy.
A group of thirty-one patients was recruited who were clinically and pathologically diagnosed with high-grade gliomas. The sequencing of 324 genes related to different types of cancer was performed to detect mutations. Subsequently, a statistical analysis was conducted to determine the mutated genes that were most related to resistance to treatment.
According to the Stupp protocol and metronomic dose of the temozolomide treatment, the mutated genes related to the second relapse of patients with high-grade glioma were , , , and .
Considering the results obtained, we suggest that mutations in the four genes and methylation of the gene promoter that codes for the MGMT protein could be related to response to treatment with temozolomide.
高级别胶质瘤患者的治疗包括肿瘤手术切除、放疗和替莫唑胺化疗。然而，由于O-甲基鸟嘌呤-DNA甲基转移酶（MGMT）的甲基化逆转机制，一些患者对替莫唑胺无反应。在接受替莫唑胺治疗的患者中，这种生物标志物已被用作预后因素。然而，并非所有患者的反应都相同，这表明存在其他参与对替莫唑胺化疗耐药的蛋白质。
招募了一组31例临床和病理诊断为高级别胶质瘤的患者。对与不同类型癌症相关的324个基因进行测序以检测突变。随后进行统计分析以确定与治疗耐药最相关的突变基因。
根据Stupp方案和替莫唑胺治疗的节拍剂量，与高级别胶质瘤患者第二次复发相关的突变基因为 、 、 和 。
考虑到所获得的结果，我们认为这四个基因的突变以及编码MGMT蛋白的基因启动子的甲基化可能与对替莫唑胺治疗的反应有关。
