High incidence of MGMT promoter methylation in primary glioblastomas without correlation with TP53 gene mutations

Jesień-Lewandowicz, Emilia; Jesionek-Kupnicka, Dorota; Zawlik, Izabela; Szybka, Malgorzata; Kulczycka-Wojdala, Dominika; Rieske, Piotr; Sieruta, Monika; Jaskólski, Dariusz J.; Och, Waldemar; Skowronski, Wiesław; Sikorska, Beata; Potemski, Piotr; Papierz, W; Liberski, Paweł P.; Kordek, Radzisław

doi:10.1016/j.cancergencyto.2008.09.015

Cited by 29 publications

(31 citation statements)

References 30 publications

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“…In our previous study, MGMT promoter methylation had no prognostic value in glioblastoma patients who were treated only with surgery and radiotherapy [8]. With regards to MGMT methylation status and the occurrence of EGFR amplification, the group of glioblastoma that shows no hypermethylation with amplification constituted about 19% of cases and the same percentage was a group with hypermethylation and amplification.…”

Section: Introductionmentioning

confidence: 83%

“…According to the classical model of the molecular GB pathway, primary glioblastoma is characterized by high incidence of EGFR amplification (about 40%) and low frequency of IDH1 mutations (< 5%); additionally, TP53 mutations are less frequent in primary GB [26,27]. To ascertain that the tumors studied were primary glioblastomas we used the following molecular criteria: frequencies of EGFR amplification (37.5%), IDH1 mutation (2.4%), and TP53 mutation (26.2%); the results were partly published before (EGFR amplification and TP53 mutations) [8]. Moreover, the 1p/19q co-deletion was infrequent (3 cases), and in 2 of these cases there was no co-presentation with IDH1 mutation (one of these cases was not determined for IDH1 mutation), which is typical for primary glioblastoma without an oligodendroglial component [11] (Table I).…”

Section: Methodsmentioning

confidence: 99%

“…Four genomic regions of the TP53 gene (exons 5-8) were amplified by PCR, as described previously [8]. Sequence analysis was performed by the dideoxy termination method using the SequiTherm Excel DNA Sequencing Kit (Epicentre Technologies, Madison, WI) and commercially available fluorescent-labeled primers as described previously [8].…”

Section: Tp53 Sequencing Analysismentioning

confidence: 99%

“…Sequence analysis was performed by the dideoxy termination method using the SequiTherm Excel DNA Sequencing Kit (Epicentre Technologies, Madison, WI) and commercially available fluorescent-labeled primers as described previously [8]. Products of the sequencing reaction were visualized and analyzed using a LiCor automated laser fluorescence sequencer.…”

Section: Tp53 Sequencing Analysismentioning

confidence: 99%

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Association of loss of heterozygosity with shorter survival in primary glioblastoma patients

Jesionek-Kupnicka

Szybka²,

Potemski³

et al. 2013

pjp

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Loss of heterozygosity (LOH) co-deletion 1p/19q, MGMT promoter methylation and/or IDH1 mutation generally signify a better prognosis for patients with glioma. However, the influence of 1p/19q co-deletion and the LOH on other chromosomes in primary glioblastoma on survival is still debatable. The aim of our study was to identify LOH on chromosomes 1p, 19q, 9p, 10q, 13q, and 17p, and evaluate their impact either alone or 1p/19q co-deletion or by groups of LOH on the overall survival of 42 primary glioblastoma patients without an oligodendroglial component. These patients were additionally molecularly characterized for EGFR amplification, IDH1 mutations and TP53 mutations. We assessed their influence on the overall survival of glioblastoma patients. LOH in at least one of the loci on all examined chromosomes was detected in 65% of cases and was significantly associated with shorter overall survival (hazard ratio 3.07; 95% CI: 1.29-7.31, p = 0.006). 1p/19q co-deletion was infrequent (7.14%) and had no impact on overall survival. Our results indicate that in primary glioblastoma a specific LOH group analysis may be important for the prognosis. LOH 1p/19q co-deletion is rare in glioblastoma without an oligodendroglial component and has no impact on patient survival.

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Section: Introductionmentioning

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Section: Tp53 Sequencing Analysismentioning

confidence: 99%

Section: Tp53 Sequencing Analysismentioning

confidence: 99%

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Association of loss of heterozygosity with shorter survival in primary glioblastoma patients

Jesionek-Kupnicka

Szybka²,

Potemski³

et al. 2013

pjp

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“…The relationship of MGMT promoter hypermethylation and TP53 gene mutation also has been studied in tumor progression include endometrial cancer (Nagy et al, 2014). esophageal squamous cell carcinoma (Su et al, 2014), and nervous system tumors (Bello et al, 2004), such as astrocytoma (Groenendijk et al, 2011) and glioblastoma (Jesien-Lewandowicz et al, 2009). However, the effect of their combined alternation on prognosis of patients with GBM was not clear.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of MGMT Promoter Methylation and TP53 Mutation in Glioblastomas Depends on IDH1 Mutation

Wang

Wang²,

Ma³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Asian Pac J Cancer Prev, 15 (24), 10893-10898 IntroductionGlioblastoma multiform (GBM), classified as World Health Organization (WHO) grade IV, is the most common malignant brain tumors in adults with an incidence rate of 23 per 100,000 persons (Stancheva et al., 2014). Their clinical course varies substantially, such that some patients succumb to progressive disease within weeks while others survive for a decade or more. Current treatments include surgery, radiation therapy and chemotherapy (Sathornsumetee et al., 2007;Koca et al., 2014;Pashaki et al., 2014). However, the median survival is still not optimistic. In spite of the existing classification, GBM subgroups are not homogeneous in terms of survival (Molenaar et al., 2014). Several prognostic factors have been established, including age, preoperative Karnofsky Performance Status (KPS), extent of resection, and also some molecular markers.Recently, molecular markers were shown to be helpful in predicting prognosis and treatment response. Three gene markers that have attracted most interest in this respect are mutations in the isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) gene (Stancheva et al., 2014), hypermethylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter, and complete deletion of both 1p and 19q. Abstract Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas.We investigated the prognostic significance of O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.

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Gallic acid provokes DNA damage and suppresses DNA repair gene expression in human prostate cancer PC‐3 cells

Liu

Huang³

et al. 2011

Environmental Toxicology

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Our earlier studies have demonstrated that gallic acid (GA) induced cytotoxic effects including induction of apoptosis and DNA damage and inhibited the cell migration and invasion in human cancer cells. However, GA-affected DNA damage and repair gene expressions in human prostate cancer cells are still unclear. In this study, we investigated whether or not GA induces DNA damage and inhibits DNA repair gene expression in a human prostate cancer cell line (PC-3). The results from flow cytometric assay indicated that GA decreased the percentage of viable PC-3 cells in a dose- and time-dependent manner. PC-3 cells after exposure to different doses (50, 100, and 200 μM) of GA and various periods of time (12, 24, and 48 h) led to a longer DNA migration smear (comet tail) occurred based on the single cell gel electrophoresis (comet assay). These observations indicated that GA-induced DNA damage in PC-3 cells, which also confirmed by 4,6-diamidino-2-phenylindole dihydrochloride staining and DNA agarose gel electrophoresis. Alternatively, results from real-time polymerase chain reaction assay also indicated that GA inhibited ataxia telangiectasia mutated, ataxia-telangiectasia and Rad3-related, O⁶-methylguanine-DNA methyltransferase, DNA-dependent serine/threonine protein kinase, and p53 mRNA expressions in PC-3 cells. Taken together, the present study showed that GA caused DNA damage and inhibited DNA repair genes as well as both effects may be the critical factors for GA-inhibited growth of PC-3 cells in vitro.

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High incidence of MGMT promoter methylation in primary glioblastomas without correlation with TP53 gene mutations

Cited by 29 publications

References 30 publications

Association of loss of heterozygosity with shorter survival in primary glioblastoma patients

Association of loss of heterozygosity with shorter survival in primary glioblastoma patients

Prognostic Value of MGMT Promoter Methylation and TP53 Mutation in Glioblastomas Depends on IDH1 Mutation

Gallic acid provokes DNA damage and suppresses DNA repair gene expression in human prostate cancer PC‐3 cells

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