IDH1 mutations is prognostic marker for primary glioblastoma multiforme but MGMT hypermethylation is not prognostic for primary glioblastoma multiforme

Kalkan, Rasime; Atlı, Emine İkbal; Özdemir, Muhsin; Çiftçi, Evrim; Aydın, Hasan Emre; Artan, Sevilhan; Arslantaş, Ali

doi:10.1016/j.gene.2014.10.027

Cited by 27 publications

(25 citation statements)

References 28 publications

(22 reference statements)

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“…Whereas, contradictory findings also have been reported in Turkish population where MGMT promoter methylation showed no prognostic value in primary glioblastoma. 40 The significant association of CpG methylation of RUNX3 promoter was reported with increased risk and progression in EC 20 and gastric cancer. 41 While, our study showed no significant correlation in CpG promoter methylation of RUNX3 between EC cases and controls.…”

Section: Discussionmentioning

confidence: 99%

Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

et al. 2017

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Promoter methylation reflects in the inactivation of different genes like O 6 -methylguanine-DNA methyltransferase DNA repair gene and runt-related transcription factor 3, a known tumor suppressor gene in various cancers such as esophageal cancer. The promoter methylation was evaluated for O 6 -methylguanine-DNA methyltransferase and runtrelated transcription factor 3 in CpG, CHH, and CHG context (where H is A, T, or C) by next-generation sequencing. The methylation status was correlated with quantitative messenger RNA expression. In addition, messenger RNA expression was correlated with different risk factors like tobacco, alcohol, betel nut consumption, and smoking habit. CpG methylation of O 6 -methylguanine-DNA methyltransferase promoter had a positive association in the development of esophageal cancer (p < 0.05), whereas runt-related transcription factor 3 promoter methylation showed no significant association (p = 1.0) to develop esophageal cancer. However, the non-CpG methylation, CHH, and CHG were significantly correlated with O 6 -methylguanine-DNA methyltransferase (p < 0.05) and runt-related transcription factor 3 (p < 0.05) promoters in the development of esophageal cancer. The number of cytosine converted to thymine (C→T) in O 6 -methylguanine-DNA methyltransferase promoter showed a significant correlation between cases and controls (p < 0.05), but in runt-related transcription factor 3 no such significant correlation was observed. Besides, messenger RNA expression was found to be significantly correlated with promoter hypermethylation of O 6 -methylguanine-DNA methyltransferase and runt-related transcription factor 3 in the context of CHG and CHH (p < 0.05). The CpG hypermethylation in O 6 -methylguanine-DNA methyltransferase showed positive (p < 0.05) association, whereas in runtrelated transcription factor 3, it showed contrasting negative association (p = 0.23) with their messenger RNA expression. Tobacco, betel nut consumption, and smoking habits were associated with altered messenger RNA expression of O 6 -methylguanine-DNA methyltransferase (p < 0.05) and betel nut consumption and smoking habits were associated with runt-related transcription factor 3 (p < 0.05). There was no significant association between messenger RNA expression of O 6 -methylguanine-DNA methyltransferase and runt-related transcription factor 3 with alcohol consumption (p = 0.32 and p = 0.15). In conclusion, our results suggest that an aberrant messenger RNA expression may be the outcome of

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Section: Discussionmentioning

confidence: 99%

Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

et al. 2017

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“…The DNA isolation and bisulfate modification methods were performed as described previously 6 . A LightCycler ® 480 real time PCR (Roche) device was used during implementation of the processes at this stage.…”

Section: Methodsmentioning

confidence: 99%

RARβ gene methylation is a candidate for primary glioblastoma treatment planning

et al. 2016

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Background: We screened RARβ methylation in primary glioblastoma multiforme (GBM) and the results were evaluated based on the clinical data and treatment type. Objective: The objective of this study was to find new areas for the usage of MS-HRM applications in the determination of methylation levels in primary GBM samples and it shows the association of RARβ methylation with the clinical outcome. Methods: In our study, tumor samples were collected during surgical resection by the Department of Neurosurgery. The clinical and radiologic data was carefully reviewed, compared, and evaluated with the histological results. The methylation status of RARβ was determined by using MS-HRM. Results: RARβ gene methylation was detected in 24 out of 40 cases (60%), with different quantitative methylation levels. The mean survival time was 19 months form ethylated cases and 15 months for the non-methylated cases. The survival time of the patients who received treatment was 25 months and the survival time of the patients who received radiotherapy alone or where no treatment protocol applied was 15-20 months. Therefore, a significant difference in survival rates has been observed (P<0.05). This study indicates a potential prognostic value for GBM treatment planning. Conclusion: Our study is the first study to investigate RARβ methylation in primary GBMs. We conclude that the RARβ gene could be a new prognostic and predictive candidate marker to designate the treatment protocol for primary GBMs.

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“…Favorable prognosis of IDH1 mutated patients is reported in several publications [13,14,35,36]. IDH1 mutation is not only a prognostic biomarker but also may be used as a target for immunotherapy [37].…”

Section: All Patientsmentioning

confidence: 98%

“…MGMT promoter methylation status is an independent favorable prognostic factor in glioblastoma patients and an important predictive biomarker for temozolomide [12]. IDH1 and IDH2 mutations in glioma correlate with increased survival [13,14]. The epidermal growth factor receptor (EGFR) variant III is expressed in glioblastomas with aggressive behavior and resistance to chemotherapy and radiotherapy and its predictive usefulness for the use of targeted vaccines is still under evaluation [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Bevacizumab in high grade glioma: Is there a subgroup that benefits?

Rigakos¹,

Kyriazoglou²,

Vernadou³

et al. 2017

Hematol Med Oncol

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Background: Prognosis for patients with original glioblastoma diagnosis remains poor. Antiangiogenic therapy with Bevacizumab in first line treatment did not lead to improvement in overall survival, while progression-free survival was prolonged by 3 to 4 months, in recent phase III studies. Bevacizumab therapy in glioblastomas is not successfully associated with any prognostic biological markers. Our study investigates the correlation between the use of bevacizumab and several clinical and molecular markers measured in gliomas everyday clinical practice.

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IDH1 mutations is prognostic marker for primary glioblastoma multiforme but MGMT hypermethylation is not prognostic for primary glioblastoma multiforme

Cited by 27 publications

References 28 publications

Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

RARβ gene methylation is a candidate for primary glioblastoma treatment planning

Bevacizumab in high grade glioma: Is there a subgroup that benefits?

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