CHANGES IN THE MGMT GENE EXPRESSION IN PATIENTS WITH PRIMARY GLIOBLASTOMA AFTER RELAPSE. INFLUENCE OF CLINICAL CHARACTERISTICS AND MGMT EXPRESSION ON SURVIVAL OF PATIENTS
Background. Over the past 10–15 years, there has been a clearer understanding of the processes occurring in cells of the primary glioblastoma. However, the change in MGMT gene expression and its role after disease relapse remain understudied. Purpose: to study changes in MGMT gene expression in case...
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| Format: | Article |
| Language: | Russian |
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Russian Academy of Sciences, Tomsk National Research Medical Center
2021-06-01
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| Series: | Сибирский онкологический журнал |
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| Online Access: | https://www.siboncoj.ru/jour/article/view/1802 |
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| author | M. V. Matsko S. S. Sklyar A. Yu. Ulitin D. E. Matsko E. N. Imyanitov A. G. Ievleva V. I. Ni N. M. Volkov A. A. Zrelov A. O. Baksheeva D. V. Galkina |
| author_facet | M. V. Matsko S. S. Sklyar A. Yu. Ulitin D. E. Matsko E. N. Imyanitov A. G. Ievleva V. I. Ni N. M. Volkov A. A. Zrelov A. O. Baksheeva D. V. Galkina |
| author_sort | M. V. Matsko |
| collection | DOAJ |
| description | Background. Over the past 10–15 years, there has been a clearer understanding of the processes occurring in cells of the primary glioblastoma. However, the change in MGMT gene expression and its role after disease relapse remain understudied. Purpose: to study changes in MGMT gene expression in case of recurrent primary glioblastoma after the standard therapy; to determine influence of clinical factors and MGMt gene expression on relapse-free survival of patients. Materials and Methods. We carried out a prospective analysis of clinical and molecular genetic characteristics of 21 patients aged from 28 to 63 with primary glioblastoma before and after recurrence. Relative mRna expression of MGMT gene and mutations in IDH1/IDH2 genes were determined in surgical biopsies using PCR techniques. after the first surgery, all patients received radiation therapy (60 Gy) and chemotherapy with adjuvant temozolomide (2–18 cycles). the second-line chemotherapy was performed in 17 (80.9 %) patients, and 8 patients received (47 %, 8/17) temozolomide.Results. the relationship between the progression-free survival (PFs) and mRna expression of MGMT gene (73.5 vs 33 weeks, p=0.013) and objective response to therapy (88 vs 36 weeks, p=0.046) was found. The number of cycles of first-line chemotherapy with temozolomide influenced the duration of the first PFs (65 weeks vs 21.5 weeks, p=0,07). the first PFs was not affected by patients’ age (p=0.64), sex (p=0.17), Karnofsky performance scale index (p=0.43), extent of brain damage (p=0.41) and extent of the resection (p=0.27). after onset of relapse, mRna expression of MGMT gene remained the same, being 66.7 % (14/21). The increased expression was observed in 23.8 % (5/21) of cases, and decreased gene expression was observed in 9.5 % (2/21) of cases. the second PFs was affected by the extent of tumor resection, although there were no statistically significant differences (p=0.52). the effect of mRna expression of MGMT gene on the median second PFs was not revealed (p=0.39). no objective response to therapy was found in patients with a low mRna expression of MGMT gene. Conclusion. Recurrent glioblastoma becomes more resistant to further therapy. With the development of tumor recurrence, the predictive value of MGMT gene is lost and the role of the extent of cytoreductive surgery increases. |
| first_indexed | 2024-04-10T01:51:54Z |
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| id | doaj.art-2ffd88be1f934763882aaab2a04c4719 |
| institution | Directory Open Access Journal |
| issn | 1814-4861 2312-3168 |
| language | Russian |
| last_indexed | 2025-03-14T10:07:32Z |
| publishDate | 2021-06-01 |
| publisher | Russian Academy of Sciences, Tomsk National Research Medical Center |
| record_format | Article |
| series | Сибирский онкологический журнал |
| spelling | doaj.art-2ffd88be1f934763882aaab2a04c47192025-03-02T11:16:14ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682021-06-0120351710.21294/1814-4861-2021-20-3-5-17856CHANGES IN THE MGMT GENE EXPRESSION IN PATIENTS WITH PRIMARY GLIOBLASTOMA AFTER RELAPSE. INFLUENCE OF CLINICAL CHARACTERISTICS AND MGMT EXPRESSION ON SURVIVAL OF PATIENTSM. V. Matsko0S. S. Sklyar1A. Yu. Ulitin2D. E. Matsko3E. N. Imyanitov4A. G. Ievleva5V. I. Ni6N. M. Volkov7A. A. Zrelov8A. O. Baksheeva9D. V. Galkina10Clinical Scientific-Practical Center of Oncology; Saint-Petersburg State University; Saint-Petersburg Medico-Social InstitutePolenov Russian Neurosurgical Institute – the branch of Almazov NMRCPolenov Russian Neurosurgical Institute – the branch of Almazov NMRCClinical Scientific-Practical Center of Oncology; Saint-Petersburg State University; Saint-Petersburg Medico-Social Institute; Polenov Russian Neurosurgical Institute – the branch of Almazov NMRCI.I. Mechnikov North-Western Medical Uuniversity; N.N. Petrov NMRC of Oncology; Saint-Petersburg State Pediatric Medical UniversityN.N. Petrov NMRC of Oncology; Saint-Petersburg State Pediatric Medical UniversityN.N. Petrov NMRC of Oncology; Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of SciencesClinical Scientific-Practical Center of Oncology; Saint-Petersburg Medico-Social InstitutePolenov Russian Neurosurgical Institute – the branch of Almazov NMRCChildren’s city multidisciplinary clinical center of high medical technologies named after K.a. RauchfusaSaint-Petersburg State UniversityBackground. Over the past 10–15 years, there has been a clearer understanding of the processes occurring in cells of the primary glioblastoma. However, the change in MGMT gene expression and its role after disease relapse remain understudied. Purpose: to study changes in MGMT gene expression in case of recurrent primary glioblastoma after the standard therapy; to determine influence of clinical factors and MGMt gene expression on relapse-free survival of patients. Materials and Methods. We carried out a prospective analysis of clinical and molecular genetic characteristics of 21 patients aged from 28 to 63 with primary glioblastoma before and after recurrence. Relative mRna expression of MGMT gene and mutations in IDH1/IDH2 genes were determined in surgical biopsies using PCR techniques. after the first surgery, all patients received radiation therapy (60 Gy) and chemotherapy with adjuvant temozolomide (2–18 cycles). the second-line chemotherapy was performed in 17 (80.9 %) patients, and 8 patients received (47 %, 8/17) temozolomide.Results. the relationship between the progression-free survival (PFs) and mRna expression of MGMT gene (73.5 vs 33 weeks, p=0.013) and objective response to therapy (88 vs 36 weeks, p=0.046) was found. The number of cycles of first-line chemotherapy with temozolomide influenced the duration of the first PFs (65 weeks vs 21.5 weeks, p=0,07). the first PFs was not affected by patients’ age (p=0.64), sex (p=0.17), Karnofsky performance scale index (p=0.43), extent of brain damage (p=0.41) and extent of the resection (p=0.27). after onset of relapse, mRna expression of MGMT gene remained the same, being 66.7 % (14/21). The increased expression was observed in 23.8 % (5/21) of cases, and decreased gene expression was observed in 9.5 % (2/21) of cases. the second PFs was affected by the extent of tumor resection, although there were no statistically significant differences (p=0.52). the effect of mRna expression of MGMT gene on the median second PFs was not revealed (p=0.39). no objective response to therapy was found in patients with a low mRna expression of MGMT gene. Conclusion. Recurrent glioblastoma becomes more resistant to further therapy. With the development of tumor recurrence, the predictive value of MGMT gene is lost and the role of the extent of cytoreductive surgery increases.https://www.siboncoj.ru/jour/article/view/1802primary glioblastomaglioblastoma recurrencemutations idh1/idh2 genes, mgmt genetemozolomideprogression-free survivalextent of resection |
| spellingShingle | M. V. Matsko S. S. Sklyar A. Yu. Ulitin D. E. Matsko E. N. Imyanitov A. G. Ievleva V. I. Ni N. M. Volkov A. A. Zrelov A. O. Baksheeva D. V. Galkina CHANGES IN THE MGMT GENE EXPRESSION IN PATIENTS WITH PRIMARY GLIOBLASTOMA AFTER RELAPSE. INFLUENCE OF CLINICAL CHARACTERISTICS AND MGMT EXPRESSION ON SURVIVAL OF PATIENTS Сибирский онкологический журнал primary glioblastoma glioblastoma recurrence mutations idh1/idh2 genes, mgmt gene temozolomide progression-free survival extent of resection |
| title | CHANGES IN THE MGMT GENE EXPRESSION IN PATIENTS WITH PRIMARY GLIOBLASTOMA AFTER RELAPSE. INFLUENCE OF CLINICAL CHARACTERISTICS AND MGMT EXPRESSION ON SURVIVAL OF PATIENTS |
| title_full | CHANGES IN THE MGMT GENE EXPRESSION IN PATIENTS WITH PRIMARY GLIOBLASTOMA AFTER RELAPSE. INFLUENCE OF CLINICAL CHARACTERISTICS AND MGMT EXPRESSION ON SURVIVAL OF PATIENTS |
| title_fullStr | CHANGES IN THE MGMT GENE EXPRESSION IN PATIENTS WITH PRIMARY GLIOBLASTOMA AFTER RELAPSE. INFLUENCE OF CLINICAL CHARACTERISTICS AND MGMT EXPRESSION ON SURVIVAL OF PATIENTS |
| title_full_unstemmed | CHANGES IN THE MGMT GENE EXPRESSION IN PATIENTS WITH PRIMARY GLIOBLASTOMA AFTER RELAPSE. INFLUENCE OF CLINICAL CHARACTERISTICS AND MGMT EXPRESSION ON SURVIVAL OF PATIENTS |
| title_short | CHANGES IN THE MGMT GENE EXPRESSION IN PATIENTS WITH PRIMARY GLIOBLASTOMA AFTER RELAPSE. INFLUENCE OF CLINICAL CHARACTERISTICS AND MGMT EXPRESSION ON SURVIVAL OF PATIENTS |
| title_sort | changes in the mgmt gene expression in patients with primary glioblastoma after relapse influence of clinical characteristics and mgmt expression on survival of patients |
| topic | primary glioblastoma glioblastoma recurrence mutations idh1/idh2 genes, mgmt gene temozolomide progression-free survival extent of resection |
| url | https://www.siboncoj.ru/jour/article/view/1802 |
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