ArticlePLoS genetics2011
Widespread hypomethylation occurs early and synergizes with gene amplification during esophageal carcinogenesis.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 82 papers, 1 of them a synthesis that pooled it.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Guidelines for pre-analytical conditions for assessing the methylation of circulating cell-free DNA.Clinical epigenetics · 2021Pooled it
- Myeloma is characterized by stage-specific alterations in DNA methylation that occur early during myelomagenesis.Journal of immunology (Baltimore, Md. : 1950) · 2013Trial
- Article
- Advances in epigenetic therapy for esophageal cancer.Clinical epigenetics · 2026Review
- The biology and therapeutic implications of heterogeneity in Barrett oesophagus and oesophageal adenocarcinoma.Nature reviews. Clinical oncology · 2026Review
- Advances in Epigenomic Sequencing and Their Applications in Cancer Diagnostics.Precision chemistry · 2025Review
- Nanopore sequencing-derived methylation biomarker prediction for methylation-specific PCR in patients with head and neck squamous cell carcinoma.Clinical epigenetics · 2025Article
- Review
- Mining nucleic acid "omics" to boost liquid biopsy in cancer.Cell reports. Medicine · 2024Review
- Hierarchical classification-based pan-cancer methylation analysis to classify primary cancer.BMC bioinformatics · 2023Article
- Review
- Epigenetic Alterations from Barrett's Esophagus to Esophageal Adenocarcinoma.International journal of molecular sciences · 2023Review
- Article
- Tracking the evolution of esophageal squamous cell carcinoma under dynamic immune selection by multi-omics sequencing.Nature communications · 2023Article
- Longitudinal monitoring of cell-free DNA methylation in ALK-positive non-small cell lung cancer patients.Clinical epigenetics · 2022Article
- Enhancement of DNA hypomethylation alterations by gastric and bile acids promotes chromosomal instability in Barrett's epithelial cell line.Scientific reports · 2022Article
- Epigenetic inactivation of DNA repair genes as promising prognostic and predictive biomarkers in urothelial bladder carcinoma patients.Molecular genetics and genomics : MGG · 2022Article
- Article
- Multi-omic cross-sectional cohort study of pre-malignant Barrett's esophagus reveals early structural variation and retrotransposon activity.Nature communications · 2022Article
- Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedMeltzer, Stephen [corrected to Meltzer, Stephen J]
Authors and funding
25 authors at 6 institutions in 3 countries.
Funding
Abstract
Although a combination of genomic and epigenetic alterations are implicated in the multistep transformation of normal squamous esophageal epithelium to Barrett esophagus, dysplasia, and adenocarcinoma, the combinatorial effect of these changes is unknown. By integrating genome-wide DNA methylation, copy number, and transcriptomic datasets obtained from endoscopic biopsies of neoplastic progression within the same individual, we are uniquely able to define the molecular events associated progression of Barrett esophagus. We find that the previously reported global hypomethylation phenomenon in cancer has its origins at the earliest stages of epithelial carcinogenesis. Promoter hypomethylation synergizes with gene amplification and leads to significant upregulation of a chr4q21 chemokine cluster and other transcripts during Barrett neoplasia. In contrast, gene-specific hypermethylation is observed at a restricted number of loci and, in combination with hemi-allelic deletions, leads to downregulatation of selected transcripts during multistep progression. We also observe that epigenetic regulation during epithelial carcinogenesis is not restricted to traditionally defined "CpG islands," but may also occur through a mechanism of differential methylation outside of these regions. Finally, validation of novel upregulated targets (CXCL1 and 3, GATA6, and DMBT1) in a larger independent panel of samples confirms the utility of integrative analysis in cancer biomarker discovery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.