Status of O 6 -methylguanine-DNA methyltransferase [MGMT] gene promoter methylation among patients with glioblastomas from India

Nehru, Gopal Arun; Pai, Rekha; Samuel, Prasanna; Chacko, Ari G; Chacko, Geeta

doi:10.4103/0028-3886.103190

Cited by 9 publications

(7 citation statements)

References 29 publications

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“…The reason may be related to the presence of pathological heterogeneity and genetic inhomogeneity in different parts of glioblastoma tissues and clinical factors [23]–[25]. Similar results were also reported for malignant melanoma [25]–[27].…”

Section: Discussionsupporting

confidence: 68%

MGMT Promoter Methylation Correlates with an Overall Survival Benefit in Chinese High-Grade Glioblastoma Patients Treated with Radiotherapy and Alkylating Agent-Based Chemotherapy: A Single-Institution Study

et al. 2014

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Promoter methylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene has been considered a prognostic marker and has become more important in the treatment of glioblastoma. However, reports on the correlation between MGMT and clinical outcomes in Chinese glioblastoma patients are very scarce. In this study, quantitative methylation data were obtained by the pyrosequencing of tumor tissues from 128 GBM patients. The median overall survival (OS) was 13.1 months, with a 1-year survival of 45.3%. The pyrosequencing data were reproducible based on archived samples yielding data for all glioblastomas. MGMT promoter methylation was detected in 75/128 cases (58.6%), whereas 53/128 (41.4%) cases were unmethylated. Further survival analysis also revealed that methylation was an independent prognostic factor associated with prolonged OS but not with progression-free survival (PFS) (p = 0.029 and p = 0.112, respectively); the hazard radios were 0.63 (95% CI: 0.42–0.96) and 0.72 (95% CI: 0.48–1.09), respectively. These data indicated that MGMT methylation has prognostic significance in patients with newly diagnosed high-grade glioblastoma undergoing alkylating agent-based chemotherapy after surgical resection.

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Section: Discussionsupporting

confidence: 68%

MGMT Promoter Methylation Correlates with an Overall Survival Benefit in Chinese High-Grade Glioblastoma Patients Treated with Radiotherapy and Alkylating Agent-Based Chemotherapy: A Single-Institution Study

et al. 2014

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“…13,26 The postoperative treatment of spinal glioma is a complex problem for neurosurgery, and the therapeutic effect remains unsatisfactory. 22 Most researchers advocate comprehensive treatment, which includes surgical resection of the tumors, supplemented by chemotherapy and radiotherapy. 23 At present, surgical resection has been achieved at a high level, but controversy exists regarding postoperative radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Even the minor injury caused by postoperative radiotherapy for spinal glioma may lead to severe complications, such as paraplegia. 22,23 Radiation myelopathy is the most distressing problem for cancer radiotherapists, which may cause vascular occlusion, spinal cord edema, demyelination of the white matter, and even spinal cord necrosis, resulting in paraplegia, cauda equina syndrome, and so on. [3][4][5][6][7][8][9][10][11][12][13][14][15]27,28 Furthermore, there is a lack of specific therapy for radiation myelopathy.…”

Section: Discussionmentioning

confidence: 99%

“…27 It has been reported that neuronutrition, vasodilation, hyperbaric oxygen, and high dose vitamins are not effective during treatment, while high dose corticosteroids can alleviate symptoms in some patients. [3][4][5][6][7][8][9][10][11][21][22][23][24]27,28 At present, radiotherapy is generally used as an adjuvant treatment for incompletely resected spinal gliomas in China. 28 However, in recent years, based on clinical observations, some researchers consider that radiation therapy can aggravate spinal cord injury and subsequently cause serious spinal cord complications.…”

Section: Discussionmentioning

confidence: 99%

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A Prospective Clinical Study on MGMT Protein Expression and the Effect of Gene Promoter Methylation on Sensitivity to Chemotherapeutics in Spinal Glioma

Sun¹,

Fan²,

Fan

et al. 2021

JIR

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Objective The present study discusses the O6-methylguanine-DNA methyltransferase (MGMT) protein expression of spinal glioma cells and the correlation between the sensitivity of promoter methylation of the MGMT gene to chemotherapy drugs, establishes a prediction method for the sensitivity of chemotherapy drugs on spinal gliomas, providing a theoretical basis for determining the best chemotherapy regimens for clinical patients after a spinal glioma operation. Methods A total of 67 patients, who received microsurgical resection for spinal glioma from October 2010 to June 2016, were selected for the present study. Immunohistochemistry and methylation were performed after the operation. Among these patients, 47 patients with postoperative chemotherapy were assigned as the experimental group, while 20 patients without chemotherapy were designated as the control group. Results Among the 47 patients in the experimental group, 39 patients had no tumor recurrence after two years, while tumors increased and symptoms were aggravated in eight patients. The progression-free survival rate of chemotherapy was 82.9%, and the two-year survival rate was 100%. The adverse reactions of patients during chemotherapy were slight. Among the 20 patients in the control group, seven patients had no tumor recurrence, while 13 patients had increased tumor size, and the progression-free survival rate was 35.0%. Conclusion Under the guidance of MGMT immunohistochemical detection and MGMT gene promoter methylation detection after surgery, chemotherapy can effectively delay tumor recurrence, prevent a reoperation, and have good safety and tolerability. This chemotherapy regimen has good prospects.

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“…This indicated that detection of methylation status in body fluids such as serum or sputum can be an effective method for NSCLC screening or for early diagnosis. These cancer-suppressor genes include P16 [1], P53, RARβ [2], MGMT [3–5], and RASSF1A . RASSF1A , also known as ras association domain-containing protein 1 gene, is associated with the pathogenesis of a variety of cancers when there is loss or altered expression of this gene, and hypermethylation of the promoter region is known to cause RASSF1A gene loss of expression.…”

Section: Introductionmentioning

confidence: 99%

Correlation Between RASSF1A Gene Promoter Hypermethylation in Serum or Sputum and Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

et al. 2019

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Background The aim of this study was to evaluate the efficacy of RASSF1A promoter hypermethylation of serum or sputum in diagnosis of non-small cell lung cancer (NSCLC) by pooling open published data. Material/Methods Open-published studies relevant to RASSF1A promoter hypermethylation and NSCLC diagnosis were screened through Medline, EMBASE, the Cochrane Library, Web of Science, Google Scholar, and CBM. Number of cases of true positive (tp), false positive (fp), false negative (fn), and true negative (tn) by RASSF1A gene promoter hypermethylation was extracted from each of the include original studies. The combined diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve (SROC) were calculated, as was the effect size. Results Twelve studies with 826 NSCLC and 598 controls were included in the present work. The combined sensitivity and specificity were 0.45 (95%CI: 0.41–0.48) (random effects) and 0.99(95%CI: 0.98–1.00) (fixed effects) respectively. The pooled positive likelihood ratio (+LR) and negative likelihood ratio (−LR) were 20.27 (9.64–42.61) and 0.53 (0.42–0.66), respectively, through the random effects model. The combined DOR was 46.63 (95%CI: 17.30–125.65) through the fixed effects model. The AUC of the SROC was 0.9989, calculated through Moses’s model for RASSF1A promoter hypermethylation as a biomarker in diagnosis of NSCLC. Conclusions The low diagnostic sensitivity for RASSF1A gene promoter hypermethylation indicated that it is not suitable for NSCLC screening. However, the high specificity made it effective for NSCLC confirmation diagnosis, which could be used instead of pathological diagnosis.

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Status of O 6 -methylguanine-DNA methyltransferase [MGMT] gene promoter methylation among patients with glioblastomas from India

Abstract: The frequency of methylation seen in this study concurs with that reported earlier from the country. MSP was easy to perform and interpret. However, the utility of this testing system in a routine diagnostic setting is still being debated.

Cited by 9 publications

References 29 publications

MGMT Promoter Methylation Correlates with an Overall Survival Benefit in Chinese High-Grade Glioblastoma Patients Treated with Radiotherapy and Alkylating Agent-Based Chemotherapy: A Single-Institution Study

MGMT Promoter Methylation Correlates with an Overall Survival Benefit in Chinese High-Grade Glioblastoma Patients Treated with Radiotherapy and Alkylating Agent-Based Chemotherapy: A Single-Institution Study

A Prospective Clinical Study on MGMT Protein Expression and the Effect of Gene Promoter Methylation on Sensitivity to Chemotherapeutics in Spinal Glioma

Correlation Between RASSF1A Gene Promoter Hypermethylation in Serum or Sputum and Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

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