ArticlePloS one2013
Unique association between global DNA hypomethylation and chromosomal alterations in human hepatocellular carcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 38 citations in OpenAlex.
- A Comparative Analysis of the Roles of von Willebrand Factor and ADAMTS13 in Hepatocellular Carcinoma: A Bioinformatics and Microarray-Based Study.Current issues in molecular biology · 2025Article
- Article
- 3D-Epigenomic Regulation of Gene Transcription in Hepatocellular Carcinoma.Advanced genetics (Hoboken, N.J.) · 2022Article
- The Co-occurrence of Chronic Hepatitis B and Fibrosis Is Associated With a Decrease in Hepatic Global DNA Methylation Levels in Patients With Non-alcoholic Fatty Liver Disease.Frontiers in genetics · 2021Article
- Immune Phenotype and Immune Checkpoint Inhibitors for the Treatment of Human Hepatocellular Carcinoma.Cancers · 2020Review
- Epigenetic mechanisms and the hallmarks of cancer: an intimate affair.American journal of cancer research · 2020Review
- Whole Genome 5'-Methylcytosine Level Quantification in Cirrhotic HCV-Infected Egyptian Patients with and without Hepatocellular Carcinoma.International journal of genomics · 2020Article
- Prediction of the Prognosis Based on Chromosomal Instability-Related DNA Methylation Patterns of ELOVL2 and UBAC2 in PTCs.Molecular therapy. Nucleic acids · 2019Article
- Molecular Scoring of Hepatocellular Carcinoma for Predicting Metastatic Recurrence and Requirements of Systemic Chemotherapy.Cancers · 2018Article
- Prenatal airborne polycyclic aromatic hydrocarbon exposure, LINE1 methylation and child development in a Chinese cohort.Environment international · 2017Article
- Genetic alterations in hepatocellular carcinoma: An update.World journal of gastroenterology · 2016Review
- Biomarkers of genome instability and cancer epigenetics.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Characterization of copy number alterations in a mouse model of fibrosis-associated hepatocellular carcinoma reveals concordance with human disease.Cancer medicine · 2016Article
- Alteration of Epigenetic Profile in Human Hepatocellular Carcinoma and Its Clinical Implications.Liver cancer · 2014Review
Corrections and comments
- Expression of concern · 2023-01-11Conflict of Interest ·
- Expression of concern
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Global DNA hypomethylation is a characteristic feature of cancer cells that closely associates with chromosomal instability (CIN). However, the association between these characteristics during hepatocarcinogenesis remains unclear. Herein, we determined the relationship between hypomethylation and CIN in human hepatocellular carcinoma (HCC) by analyzing 179 HCCs, 178 matched non-tumor livers and 23 normal liver tissues. Hypomethylation at three different repetitive DNA (rDNA) sequences and hypermethylation of 12 CpG loci, including 11 tumor suppressor gene (TSG) promoters, were quantified using MethyLight or combined bisulfite restriction analysis. Fractional allelic loss (FAL) was used as a marker for CIN, calculated by analyzing 400 microsatellite markers. Gains and losses at each chromosome were also determined using semi-quantitative microsatellite analysis. The associations between rDNA hypomethylation and FAL, as well as between TSG hypermethylation and FAL were investigated. Significantly more hypomethylation was observed in HCC tissues than in normal liver samples. Progression of hypomethylation during carcinogenesis was more prominent in hepatitis C virus (HCV)-negative cases, which was in contrast to our previous reports of significantly increased TSG methylation levels in HCV-positive tumors. Absence of liver cirrhosis and higher FAL scores were identified as independent contributors to significant hypomethylation of rDNA in HCC. Among the chromosomal alterations frequently observed in HCC, loss of 8p, which was unique in the earliest stages of hepatocarcinogenesis, was significantly associated with hypomethylation of rDNA by multivariable analysis (p=0.0153). rDNA hypomethylation was also associated with a high FAL score regardless of tumor differentiation (p=0.0011, well-differentiated; p=0.0089, moderately/poorly-differentiated HCCs). We conclude that DNA hypomethylation is an important cause of CIN in the earliest step of HCC, especially in a background of non-cirrhotic liver.
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