ArticleClinical epigenetics2014
Quantitative methodology is critical for assessing DNA methylation and impacts on correlation with patient outcome.
Article in Clinical epigenetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Olaparib in HR-deficient, metastatic triple-negative breast and platinum-sensitive relapsed ovarian cancers without germline mutations in BRCA1/2: phase 2 EMBRACE trial.British journal of cancer · 2026Trial
- Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application.Clinical and translational medicine · 2024Review
- Temperature-Wise Calibration Increases the Accuracy of DNA Methylation Levels Determined by High-Resolution Melting (HRM).International journal of molecular sciences · 2024Article
- The role of aberrant DNA methylation in cancer initiation and clinical impacts.Therapeutic advances in medical oncology · 2024Article
- Epigenetic methylation changes: implication as biomarkers in oral and maxillofacial area cancers.Medicine and pharmacy reports · 2023Article
- Colorectal cancer patients withAging · 2020Article
- Promoter methylation status ofTranslational lung cancer research · 2019Article
- Promoter Methylation of Four Tumor Suppressor Genes in Human Papillary Thyroid Carcinoma.Iranian journal of pathology · 2019Article
- Methylation Status of Transcriptional Modulatory Genes Associated with Colorectal Cancer in Northeast China.Gut and liver · 2018Article
- DNA Methylation Levels of the ELMO Gene Promoter CpG Islands in Human Glioblastomas.International journal of molecular sciences · 2018Article
- DNA methylation profiles in cancer diagnosis and therapeutics.Clinical and experimental medicine · 2018Review
- Epigenetic dysregulation of ID4 predicts disease progression and treatment outcome in myeloid malignancies.Journal of cellular and molecular medicine · 2017Article
- EpiHRMAssay,Biology methods & protocols · 2017Article
- Genome-scale methylation assessment did not identify prognostic biomarkers in oral tongue carcinomas.Clinical epigenetics · 2016Article
- Article
- Emerging blood-based biomarkers for detection of gastric cancer.World journal of gastroenterology · 2015Review
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDNA hypermethylation is reported as a frequent event and prognostic marker in head and neck squamous cell carcinomas (HNSCC). Methylation has been commonly assessed with non-quantitative methodologies, such as methylation-specific PCR (MSP). We investigated previously reported hypermethylated genes with quantitative methodology in oral tongue squamous cell carcinomas (OTSCC).
resultsThe methylation status of 12 genes in 115 OTSCC samples was assessed by one or more of three quantitative analyses: methylation sensitive high resolution melting (MS-HRM), sensitive-melting analysis after real time-methylation specific PCR (SMART-MSP), and bisulfite pyrosequencing. In contrast to much of the literature, either no or infrequent locus-specific methylation was identified by MS-HRM for DAPK1, RASSF1A, MGMT, MLH1, APC, CDH1, CDH13, BRCA1, ERCC1, and ATM. The most frequently methylated loci were RUNX3 (18/108 methylated) and ABO (22/107 methylated). Interrogation of the Cancer Genome Atlas (TCGA) HNSCC cohort confirmed the frequency of significant methylation for the loci investigated. Heterogeneous methylation of RUNX3 (18/108) and ABO (22/107) detected by MS-HRM, conferred significantly worse survival (P = 0.01, and P = 0.03). However, following quantification of methylation levels using pyrosequencing, only four tumors had significant quantities (>15%) of RUNX3 methylation which correlated with a worse patient outcome (P <0.001), while the prognostic significance of ABO hypermethylation was lost. RUNX3 methylation was not prognostic for the TCGA cohort (P = 0.76).
conclusionsWe demonstrated the critical need for quantification of methylation levels and its impact on correlative analyses. In OTSCC, we found little evidence of significant or frequent hypermethylation of many loci reported to be commonly methylated. It is likely that previous reports have overestimated the frequency of significant methylation events as a consequence of the use of non-quantitative methodology.
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