Promoter methylation of AREG, HOXA11, hMLH1, NDRG2, NPTX2 and Tes genes in glioblastoma

Skiriutė, Daina; Vaitkienė, Paulina; Ašmonienė, Virginija; Steponaitis, Giedrius; Deltuva, Vytenis Pranas; Tamašauskas, Arimantas

doi:10.1007/s11060-013-1133-3

Cited by 29 publications

(26 citation statements)

References 34 publications

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“…Further survival analysis in this study, in which we included tumors of different malignancy grade, demonstrated significant correlation between NDRG2 promoter methylation and poor patient outcome (Figure 1B). This is in contrast to earlier findings 5, 22, where studies on NDRG2 promoter methylation and patient survival have been done with the focus on glioblastoma alone.…”

Section: Discussioncontrasting

confidence: 94%

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Glioma Malignancy-Dependent NDRG2 Gene Methylation and Downregulation Correlates with Poor Patient Outcome

Skiriutė¹,

Steponaitis²,

Vaitkienė³

et al. 2014

J. Cancer

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Aims: NDRG2 (N-myc downstream regulated gene 2) gene is involved in important biological processes: cell differentiation, growth and apoptosis. Several molecular studies have shown NDRG2 as a promising diagnostic marker involved in brain tumor pathology. The aim of the study was to investigate how changes in epigenetic modification and activity of NDRG2 reflect on glioma malignancy and patient outcome. Methods: 137 different malignancy grade gliomas were used as the study material: 14 pilocytic astrocytomas grade I, 45 diffuse astrocytomas grade II, 29 anaplastic astrocytomas grade III, and 49 grade IV astrocytomas (glioblastomas). Promoter methylation analysis has been carried out by using methylation-specific PCR, whereas RT-PCR and Western-blot analyses were used to measure NDRG2 expression levels. Results: We demonstrated that NDRG2 gene methylation frequency increased whereas expression at both mRNA and protein levels markedly decreased in glioblastoma specimens compared to the lower grade astrocytomas. NDRG2 transcript and protein levels did not correlate with the promoter methylation state, suggesting the presence of alternative regulatory gene expression mechanisms that may operate in a tissue-specific manner in gliomas. Kaplan-Meier analyses revealed significant differences in survival time in gliomas stratified by NDRG2 methylation status and mRNA and protein expression levels. Conclusions: Our findings highlight the usefulness of combining epigenetic data to gene expression patterns at mRNA and protein level in tumor biomarker studies, and suggest that NDRG2 downregulation might bear influence on glioma tumor progression while being associated with higher malignancy grade.

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Section: Discussioncontrasting

confidence: 94%

“…With particular regard to glioma, recent clinical studies demonstrated NDRG2 as a putative tumor suppressor gene silenced in the majority of glioblastomas 5, 7, 22. However, the main mechanism that underlies NDRG2 silencing in glioma is unknown.…”

Section: Introductionmentioning

confidence: 99%

Glioma Malignancy-Dependent NDRG2 Gene Methylation and Downregulation Correlates with Poor Patient Outcome

Skiriutė¹,

Steponaitis²,

Vaitkienė³

et al. 2014

J. Cancer

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“…Progression free survival (PFS) was also higher among methylated than among unmethylated patients (13.3 months vs. 7.8 months) [95]. This is in agreement with results of another study that showed MGMT methylation was correlated with better survival of treated GBM patients with a hazard ratio (HR) of 0.61 [96]. Moreover the median OS among GBM patients with methylated MGMT promoter tumors was 19 months compared with 13 months in patients with unmethylated MGMT promoter tumors and the median PFS was 8 months for the methylated MGMT promoter status compared with 6 months for the unmethylated MGMT promoter status [97].…”

Section: Dna Repair Gene Methylation Status As Biomarkersupporting

confidence: 87%

Methylation of DNA repair genes and the efficacy of DNA targeted anticancer treatment

Julsing¹,

Peters²

2014

Oncol Discov

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Cancer is considered both a genetic and epigenetic disease. The best studied epigenetic mechanism in carcinogenesis is DNA methylation, a mechanism which inactivates tumor suppressor genes by methylating their promoters. A subclass of tumor suppressor genes that are often methylated in the process of carcinogenesis are the DNA repair genes. Accumulation of DNA damage is associated with cancer and thus inactivation of DNA repair genes promotes cancer formation. Methylation of DNA repair genes seems to be unique compared to the methylation of other tumor suppressor genes in that it not only promotes tumorigenesis, but at the same time influences the sensitivity of tumors to chemotherapies that are based on agents that damage DNA to kill cancer cells. This literature study summarizes the current knowledge regarding epigenetic inactivation of DNA repair genes and the subsequent progress that has been made coping with the acquired chemotherapy resistances.

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“…Two sets of primers targeting the CpG island near the transcription start site in the promoter region of HOXA11 [12] were employed to evaluate the methylation status in naive MCF-7 and MDA-MB-231 cells (Figure 2A). The promoter region was completely methylated in MDA-MB-231 cells and partially methylated in MCF-7 cells.…”

Section: Resultsmentioning

confidence: 99%

“…The methylated primers were as follows: forward primer, 5′-GTTTACGGTGTTATAGAAATTGGAC-3′; reverse primer, 5′-GTACACAAAAACTACCTACAAACGC-3′; product length, 129bp. The unmethylated primers were as follows: forward primer, 5′-TTTATGGTGTTATAGAAATTGGATGA-3′; reverse primer, 5′-TCATACACAAAAACTACCTACAAACAC-3′; product length, 130bp [12]. A total of 35 cycles were run with an annealing temperature of 55°C.…”

Section: Methodsmentioning

confidence: 99%

Homeobox A11 hypermethylation indicates unfavorable prognosis in breast cancer

et al. 2016

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Homeobox A11 (HOXA11) is one of the hypermethylated genes in breast cancer and its function in breast tumorigenesis remains elusive. In this study, we analyzed the methylation status of HOXA11 in 264 paired breast cancer and normal tissue as well as in matched serum samples by MethyLight assay. Further, the function of HOXA11 in breast tumorigenesis was analyzed by cell proliferation and migration assays. We found that HOXA11 was hypermethylated in cancer tissues (45.08%), especially in invasive ductal carcinomas (P<0.001), patients with a family history of cancer (P=0.033), cases with metastatic lymph nodes (P=0.004) and P53 positive group (P=0.017). Kaplan-Meier survival analysis and Cox regression analysis revealed that HOXA11 hypermethylation is an independent predictor of poor outcomes. The over expression of HOXA11 suppressed cell growth in MDA-MB-231, MCF7, SKBR3 and BT474 cells. In conclusion, the hypermethylation of HOXA11 is an independent prognostic biomarker in breast cancer. Additionally, HOXA11 can be a potential tumor suppressor.

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Promoter methylation of AREG, HOXA11, hMLH1, NDRG2, NPTX2 and Tes genes in glioblastoma

Cited by 29 publications

References 34 publications

Glioma Malignancy-Dependent NDRG2 Gene Methylation and Downregulation Correlates with Poor Patient Outcome

Glioma Malignancy-Dependent NDRG2 Gene Methylation and Downregulation Correlates with Poor Patient Outcome

Methylation of DNA repair genes and the efficacy of DNA targeted anticancer treatment

Homeobox A11 hypermethylation indicates unfavorable prognosis in breast cancer

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