Mutations in the PIK3C2B , ERBB3 , KIT , and MLH1 Genes and Their Relationship with Resistance to Temozolomide in Patients with High-Grade Gliomas

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...

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Published in:Biomedicines 2024-12, Vol.12 (12), p.2777
Main Authors: 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
Format: Article
Language:English
Subjects:
Amino acids
Bioinformatics
Brain cancer
Cancer
Care and treatment
Chemotherapy
Classification
DNA methylation
DNA methyltransferase
Enzymes
ErbB-3 protein
Gene mutations
Genes
Genetic aspects
Glioma
Gliomas
Methylation
Methylguanine
MLH1 protein
Molecular biology
Mortality
Mutation
Nervous system
O6-methylguanine-DNA methyltransferase
Patients
Prognosis
Proteins
Radiation therapy
radiotherapy
resistance
Statistical analysis
Temozolomide
Tissues
Tumors
Variables
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Summary: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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines12122777