TY - JOUR
T1 - Mutations in the PIK3C2B, ERBB3, KIT, and MLH1 Genes and Their Relationship with Resistance to Temozolomide in Patients with High-Grade Gliomas
AU - Ortiz Gómez, León Darío
AU - Contreras Martínez, Heidy Johanna
AU - Galvis Pareja, David Andrés
AU - Vélez Gómez, Sara
AU - Salazar Flórez, Jorge Emilio
AU - Monroy, Fernando P.
AU - Peláez Sánchez, Ronald Guillermo
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/12
Y1 - 2024/12
N2 - Introduction. 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 O6-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. Methods. 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. Results. 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 PIK3C2B, KIT, ERBB3, and MLH1. Conclusions. 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.
AB - Introduction. 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 O6-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. Methods. 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. Results. 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 PIK3C2B, KIT, ERBB3, and MLH1. Conclusions. 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.
KW - cancer
KW - chemotherapy
KW - gliomas
KW - mutations
KW - radiotherapy
KW - resistance
KW - temozolomide
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U2 - 10.3390/biomedicines12122777
DO - 10.3390/biomedicines12122777
M3 - Article
AN - SCOPUS:85213219196
SN - 2227-9059
VL - 12
JO - Biomedicines
JF - Biomedicines
IS - 12
M1 - 2777
ER -