Relationships between &lt;em&gt;MGMT&lt;/em&gt; promoter methylation and gastric cancer: a meta-analysis

Yu, Dan; Cao, Tao; Han, Ya‐di; Huang, Feng

doi:10.2147/ott.s114052

Cited by 7 publications

(4 citation statements)

References 53 publications

(41 reference statements)

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“…Gene silencing and loss of expression of MGMT, tumor suppressor gene, was reported in various types of cancers including breast cancer, colorectal cancer, nonsmall-cell lung cancer, melanoma, gliomas, and gastric cancer that is not related to gene mutations, deletions, rearrangements, or RNA instability. 37,38 Hypermethylation in specific region of promoter was suggested as one of the possible mechanisms for MGMT gene silencing in various cancers. 10,11 In the case of breast cancer, the earlier studies have estimated the frequency of MGMT promoter methylation between 22% and 32%.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic modulation of BRCA‐1 and MGMT genes, and histones H4 and H3 are associated with breast tumors

Paydar

Asadikaram

Nejad

et al. 2019

J of Cellular Biochemistry

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Aberrant patterns in promoter methylation of tumor-suppressor genes and posttranslational modifications of histone proteins are considered as major features of malignancy. In this study, we aimed to investigate promoter methylation of three tumor-suppressor genes (BRCA-1, MGMT, and P16) and three histone marks (H3K9ac, H3K18ac, and H4K20me3) in patients with breast tumors. This case-control study included 27 patients with malignant breast tumors (MBT) and 31 patients with benign breast tumors (BBT). The methylation-specific PCR was used for determining promoter methylation of BRCA-1, MGMT, and P16 genes. Western blot analysis was performed to detect histone lysine acetylation (H3K9ac and H3K18ac) and lysine methylation (H4K20me3). BRCA-1 promoter methylation was detected in 44.4% of the MBT whereas this alteration was found in 9.7% of BBT (P = 0.005). The Kaplan-Meier analysis indicated that hypermethylation in BRCA-1 promoter was significantly associated with poor overall survival of patients with breast cancer (P = 0.039). MGMT promoter methylation was identified in 18.5% of MBT and 0.0% of the BBT (P = 0.01). The frequency of P16 promoter methylation was 25.8% in BBT and 11.1% in MBT (P = 0.12). As compared with BBT, MBT samples displayed the aberrant patterns of histones marks with hypomethylation of H4K20 and hypoacetylation of H3K18 (P = 0.03 and P = 0.04, respectively). There was a negative significant correlation between H3K9ac levels and tumor size in MBT group (r = −0.672; P = 0.008). The present findings suggest that promoter hypermethylation of MGMT and BRCA-1 genes along with alterations in H3K18ac and H4K20me3 levels may have prognostic values in patients with breast cancer. Moreover, the detection of these epigenetic modifications in breast tumors could be helpful in finding new methods for breast cancer therapy. K E Y W O R D S breast cancer, breast tumor, epigenetic, histone modification, promoter methylation, tumor suppressor J Cell Biochem. 2019;120:13726-13736. wileyonlinelibrary.com/journal/jcb 13726 |

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Section: Discussionmentioning

confidence: 99%

Epigenetic modulation of BRCA‐1 and MGMT genes, and histones H4 and H3 are associated with breast tumors

Paydar

Asadikaram

Nejad

et al. 2019

J of Cellular Biochemistry

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“…Promoter methylation of MGMT is related to gastric cancer risk, distant metastasis, and lymph node metastasis, which indicates that MGMT promoter methylation may play an important role in gastric cancer development [ 67 ]. Promoter methylation of ASC/TMS1 is associated with poor prognosis of patients with gastric cancer [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies

et al. 2017

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Clinically useful molecular tools to triage gastric cancer patients are not currently available. We aimed to develop a molecular tool to predict gastric cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer clinics in low resource settings.We discovered and validated a DNA methylation biomarker panel in endoscopic samples obtained from 362 patients seen between 2004 and 2009 in three high-risk gastric cancer clinics in Lima, Perú, and validated it in 306 samples from the Cancer Genome Atlas project (“TCGA”). Global, epigenome wide and gene-specific DNA methylation analyses were used in a Phase I Biomarker Development Trial to identify a continuous biomarker panel that combines a Global DNA Methylation Index (GDMI) and promoter DNA methylation levels of IRF4, ELMO1, CLIP4 and MSC.We observed an inverse association between the GDMI and histological progression to gastric cancer, when comparing gastritis patients without metaplasia (mean = 5.74, 95% CI, 4.97−6.50), gastritis patients with metaplasia (mean = 4.81, 95% CI, 3.77−5.84), and gastric cancer cases (mean = 3.38, 95% CI, 2.82−3.94), respectively (p < 0.0001). Promoter methylation of IRF4 (p < 0.0001), ELMO1 (p < 0.0001), CLIP4 (p < 0.0001), and MSC (p < 0.0001), is also associated with increasing severity from gastritis with no metaplasia to gastritis with metaplasia and gastric cancer.Our findings suggest that IRF4, ELMO1, CLIP4 and MSC promoter methylation coupled with a GDMI>4 are useful molecular tools for gastric cancer risk stratification in endoscopic biopsies.

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“…Sawnhey et al, observed that increased risk of nodal infiltration is associated with MGMT methylation in oral cancer (Sawhney et al, 2012). Additionally, Yu and coworkers demonstrated that MGMT methylation increases the risk of nodal metastases in gastric cancer (Yu et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

The role of MGMT polymorphisms (Rs12917 and Rs11016879) in head and neck cancer risk and prognosis

et al. 2018

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Head and neck squamous cell carcinoma (HNSCC) is one of the leading cancers by incidence worldwide. The risk of these cancers is strictly associated with alkylation factors present in tobacco smoke. The crucial role in preventing DNA alkylation is played by O-methylguanine-DNA methyltransferase (MGMT). Dysfunction or lack of MGMT is associated with an increased risk of cancer. The aim of the study was to assess the influence of MGMT polymorphisms: rs12917 and rs11016879 on HNSCC risk and course. The study consisted of 69 HNSCC patients and 242 healthy individuals. Case samples were taken from resected tumour tissue. The control group comprised samples of epithelial cells collected from mucous membranes using swabs. DNA samples were genotyped by employing the 5' nuclease assay for allelic discrimination using TaqMan SNP Genotyping Assays. The significance between distributions of genotypes and alleles was tested using Pearson's χ test analysis. Our results indicated that the MGMT rs12917 TT genotype increases the risk of HNSCC. The MGMT rs11016879 AG genotype and A allele were associated with increased HNSCC risk. We noted higher risk of nodal metastasis in rs11016879 AA homozygotes. Mechanisms leading to MGMT enzymatic defect are unknown and hence further studies need to be carried out. Our data suggest that the examined polymorphisms may be considered as potential prognostic factors for HNSCC risk and outcome. Further studies are necessary to verify our results.

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Relationships between <em>MGMT</em> promoter methylation and gastric cancer: a meta-analysis

Cited by 7 publications

References 53 publications

Epigenetic modulation of BRCA‐1 and MGMT genes, and histones H4 and H3 are associated with breast tumors

Epigenetic modulation of BRCA‐1 and MGMT genes, and histones H4 and H3 are associated with breast tumors

Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies

The role of MGMT polymorphisms (Rs12917 and Rs11016879) in head and neck cancer risk and prognosis

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