scholarly journals Prognostic value of test(s) for O6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide

2019 ◽  
Author(s):  
Alexandra McAleenan ◽  
Amy Howell ◽  
Ashleigh Kernohan ◽  
Claire L Faulkner ◽  
Sarah Dawson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Promoter Methylation ◽  
Prognostic Value ◽  
Dna Methyltransferase ◽  
Mgmt Promoter Methylation ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Promoter

Correlations Between O6-Methylguanine DNA Methyltransferase Promoter Methylation Status, 1p and 19q Deletions, and Response to Temozolomide in Anaplastic and Recurrent Oligodendroglioma: A Prospective GICNO Study

2006 ◽  
Vol 24 (29) ◽  
pp. 4746-4753 ◽  
Author(s):  
Alba A. Brandes ◽  
Alicia Tosoni ◽  
Giovanna Cavallo ◽  
Michele Reni ◽  
Enrico Franceschi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Promoter Methylation ◽  
Dna Methyltransferase ◽  
Response Rate ◽  
Methylation Status ◽  
Mgmt Promoter Methylation ◽  
Allelic Loss ◽  
Methylguanine Dna Methyltransferase ◽  
Oligodendroglial Tumors ◽  
Mgmt Promoter

Purpose To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting. Patients and Methods From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction. Results The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09). Conclusion TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.

Clinical Significance of O-6-Methylguanine-DNA-Methyltransferase Promoter Methylation in Patients with Esophageal Carcinoma: A Systematic Meta-Analysis

2017 ◽  
Vol 36 (2) ◽  
pp. 89-97 ◽  
Author(s):  
Yan Zhang ◽  
Ti Tong
Keyword(s):  
Esophageal Carcinoma ◽  
Promoter Methylation ◽  
Dna Methyltransferase ◽  
Meta Analysis ◽  
Clinical Stage ◽  
Mgmt Promoter Methylation ◽  
Lymph Node Status ◽  
Tissue Samples ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Promoter

Background: The correlation between O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and esophageal cancer remains controversial. This study was conducted to evaluate the clinical effect of MGMT promoter methylation on esophageal carcinoma patients. Methods: A literature search was conducted in the PubMed, EMBASE, EBSCO, and Cochrane Library databases. The overall OR and corresponding 95% CI were calculated using the random-effects model. Results: Finally, 17 eligible studies were identified in this meta-analysis; these studies included a total of 1,368 patients with esophageal carcinoma and 1,489 with nonmalignant controls. MGMT promoter methylation was significantly higher in esophageal carcinoma tissue samples than in nonmalignant tissue samples (OR 3.64, p < 0.001). Promoter methylation of the MGMT gene was not associated with gender, cigarette smoking, drinking behavior, or tumor differentiation, but MGMT promoter methylation was correlated with age (≥60 vs. <60 years: OR 1.64, p = 0.028), lymph node status (positive status vs. negative status: OR 2.39, p = 0.024), and clinical stage (stages 3-4 vs. 1-2: OR 10.59, p < 0.001). Conclusions: Our findings suggest that MGMT promoter methylation may be correlated with esophageal cancer carcinogenesis and could be associated with age, lymph node status, and clinical stage.

scholarly journals Tim-3 protein expression with MGMT methylation status in glioblastoma and association with survival

2020 ◽  
Author(s):  
ji zhang ◽  
Xiaoli Wang ◽  
Shengquan Ye ◽  
Lijiao Liang ◽  
Yi Zhou ◽  
...  
Keyword(s):  
Protein Expression ◽  
Promoter Methylation ◽  
Immune Checkpoint ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Mgmt Promoter Methylation ◽  
Mgmt Methylation ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Promoter

Abstract Background Understanding the molecular landscape of glioblastoma (GBM) is increasingly crucial for its therapy. Immune checkpoint molecules motivated the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecule T cell immunoglobulin mucin-3 (Tim-3) on tumor-infiltrating immune cells (TIICs) and O-6-Methylguanine-DNA methyltransferase (MGMT) methylation status remains to be fully elucidated. We aimed to develop an MGMT methylation status-associated immune prognostic signature for predicting prognosis in GBMs.Patients and Methods: A total of 84 patients with newly diagnosed GBM were involved. MGMT methylation status was retrospectively analyzed and the expression level of Tim-3 protein was investigated using immunohistochemistry (IHC). The correlation between Tim-3 protein expression and MGMT methylation status, and the prognosis was explored.Results The obtained data showed that Tim-3 protein was expressed at different levels in GBMs. Mesenchymal expression of Tim-3 protein in these tissues was 73.81% (62/84), including low 15.48% (13/84), moderate 7.14% (6/84) and strong expression 51.19% (43/84), respectively. Of the 48 patients whose tumors tested positive for MGMT methylation, the remaining 36 patients was negative.Conclusions We profiled the immune status in GBM with MGMT promoter methylation and established a local immune signature for GBM, which could independently identify patients with a favorable prognosis, indicating the relationship between prognosis and immune. MGMT promoter methylation with lower Tim-3 protein expression was statistically significantly associated with better survival.

Correlation of the quantitative level of MGMT promoter methylation and overall survival in primary diagnosed glioblastomas using the quantitative MethyQESD method

2019 ◽  
Vol 73 (2) ◽  
pp. 112-115 ◽  
Author(s):  
Charlotte von Rosenstiel ◽  
Benedikt Wiestler ◽  
Bernhard Haller ◽  
Friederike Schmidt-Graf ◽  
Jens Gempt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Promoter Methylation ◽  
Promoter Region ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Mgmt Promoter Methylation ◽  
Newly Diagnosed ◽  
Quantitative Level ◽  
Mgmt Promoter ◽  
The Impact

AimsO(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is a high predictive factor for therapy results of temozolomide in patients with glioma. The objective of this work was to analyse the impact of MGMT promoter methylation in patients with primary diagnosed glioblastoma (GBM) relating to survival using a quantitative method (methylation quantification of endonuclease-resistant DNA, MethyQESD) by verifying a cut-off point for MGMT methylation provided by the literature (</≥10%) and calculating an optimal cut-off.Methods67 patients aged 70 years or younger, operated between January 2013 and December 2015, with newly diagnosed IDH wild-type GBM and clinical follow-up were retrospectively investigated in this study. A known MGMT promoter methylation status was the inclusion criteria.ResultsMedian overall survival (OS) was 16.9 months. Patients who had a methylated MGMT promoter region of ≥10% had an improved OS compared with patients with a methylated promoter region of <10% (p=0.002). Optimal cut-off point for MGMT promoter methylation was 11.7% (p=0.012).ConclusionThe results confirm that the quantitative level of MGMT promoter methylation is a positive prognostic factor in newly diagnosed patients with GBM. The cut-off provided by the literature (</≥10%) and the calculated optimal cut-off value of 11.7% give a statistically significant separation. Hence, MethyQESD is a reliable method to calculate MGMT promoter methylation in GBM.

Determination of O-6-methylguanine-DNA methyltransferase by immunochemistry and pyrosequencing as a predictive factor of response to temozolomide in pancreatic neuroendocrine tumors.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 195-195
Author(s):  
Roberto Escala ◽  
L Miguel Navarro ◽  
Sofía Del Carmen Martínez ◽  
Sandra I Malmierca Gonzalez ◽  
Julia Ayuso Martín-Romo ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Predictive Factor ◽  
Promoter Methylation ◽  
Predictive Value ◽  
Dna Methyltransferase ◽  
Predictive Power ◽  
Mgmt Promoter Methylation ◽  
Pancreatic Neuroendocrine Tumors ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Promoter

195 Background: Temozolomide (TMZ) is an alkylating agent that has shown good results in the treatment of neuroendocrine and central nervous system (CNS) tumors. The loss of O-6-methylguanine-DNA methyltransferase (MGMT) expression by pyrosequencing (PSQ) is a predictive factor of response to treatment with TMZ in high-grade gliomas. However, its predictive value in pancreatic neuroendocrine tumors (pNET) is controversial, and there is no consensus on how to best assess MGMT. The aim was to evaluate the objective response rate in pNET according to the state of MGMT, assessed by PSQ for evaluation of promoter methylation and immunohistochemistry (IHC). Methods: Patients with pNET who were treated with TMZ at the center between 2008 and 2017 were studied retrospectively. Ten patients were included in the study. A deficiency of MGMT was determined by IHC and MGMT promoter methylation by PSQ. For IHC, the cut-off was 10%, defined as negative < 10% of tumor cells positive in the tumor tissue. For the PSQ, the cut-off was 8%, defined as methylated who presented > 8%. Results: A deficiency of MGMT was detected in five patients (50%) by IHC. An MGMT promoter methylation by PSQ was observed in three patients (30%). The IHC results were consistent with PSQ results in only six patients (60%); one patient with methylated MGMT had positive IHC, and three patients had unmethylated MGMT by PSQ unmethylated, IHC negative. PSQ had a high positive predictive value of response because the three patients with MGMT promoter methylation by PSQ presented objective responses (OR). Nevertheless, a low negative predictive power (57%) was observed because three of seven patients with unmethylated MGMT presented OR. Of the five patients with MGMT deficiency by IHC, four (80%) presented OR, suggesting positive predictive value of 80%; however, it also presented a low negative predictive power of 60%. Conclusions: Despite having 100% of the patients with MGMT promoter methylation showing OR in this series, the low negative predictive power suggests that the absence of MGMT deficiency by IHC or MGMT unmethylated by PSQ does not contraindicate the use of TMZ in pNET treatment.

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