ArticlePloS one2014
Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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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
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- Prognostic DNA methylation markers for hormone receptor breast cancer: a systematic review.Breast cancer research : BCR · 2020Pooled it
- Comparative Diagnostic Accuracy of Contrast-Enhanced Ultrasound and Shear Wave Elastography in Differentiating Benign and Malignant Lesions: A Network Meta-Analysis.Frontiers in oncology · 2019Pooled it
- Computational Framework for High Copy-Number Probe Selection and Cross-Binding Reduction.Analytical science advances · 2025Article
- Methylation of LINE-1 and Alu repetitive sequence in keloid.Scientific reports · 2025Article
- Global Hypomethylation as Minimal Residual Disease (MRD) Biomarker in Esophageal and Esophagogastric Junction Adenocarcinoma.Cancers · 2025Article
- Exploring transposable elements: new horizons in cancer diagnostics and therapeutics.Mobile DNA · 2025Review
- The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment.Current oncology (Toronto, Ont.) · 2025Review
- Article
- Ketone body, as an emerging modulator of metabolic reprogramming and epigenetics in breast cancer.Iranian journal of basic medical sciences · 2025Review
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- Alterations of senescence-associated markers in patients with non-syndromic cleft lip and palate.Scientific reports · 2024Article
- Prospects for breast cancer immunotherapy using microRNAs and transposable elements as objects.Exploration of targeted anti-tumor therapy · 2024Review
- Current Advances in Breast Cancer: Implications for Developing New Treatment Strategies Through Epi-Drugs on the Road to Modifying the Epigenome.Journal of clinical practice and research · 2023Review
- Alu RNA fold links splicing with signal recognition particle proteins.Nucleic acids research · 2023Article
- Influence of the Mediterranean Diet on Healthy Aging.International journal of molecular sciences · 2023Review
- Gene body methylation in cancer: molecular mechanisms and clinical applications.Clinical epigenetics · 2022Review
- Article
- Role of Transposable Elements in Genome Stability: Implications for Health and Disease.International journal of molecular sciences · 2022Review
- The Utility of Repetitive Cell-Free DNA in Cancer Liquid Biopsies.Diagnostics (Basel, Switzerland) · 2022Review
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The changes in DNA methylation status in cancer cells are characterized by hypermethylation of promoter CpG islands and diffuse genomic hypomethylation. Alu and long interspersed nucleotide element-1 (LINE-1) are non-coding genomic repetitive sequences and methylation of these elements can be used as a surrogate marker for genome-wide methylation status. This study was designed to evaluate the changes of Alu and LINE-1 hypomethylation during breast cancer progression from normal to pre-invasive lesions and invasive breast cancer (IBC), and their relationship with characteristics of IBC. We analyzed the methylation status of Alu and LINE-1 in 145 cases of breast samples including normal breast tissue, atypical ductal hyperplasia/flat epithelial atypia (ADH/FEA), ductal carcinoma in situ (DCIS) and IBC, and another set of 129 cases of IBC by pyrosequencing. Alu methylation showed no significant changes during multistep progression of breast cancer, although it tended to decrease during the transition from DCIS to IBC. In contrast, LINE-1 methylation significantly decreased from normal to ADH/FEA, while it was similar in ADH/FEA, DCIS and IBC. In IBC, Alu hypomethylation correlated with negative estrogen receptor (ER) status, and LINE-1 hypomethylation was associated with negative ER status, ERBB2 (HER2) amplification and p53 overexpression. Alu and LINE-1 methylation status was significantly different between breast cancer subtypes, and the HER2 enriched subtype had lowest methylation levels. In survival analyses, low Alu methylation status tended to be associated with poor disease-free survival of the patients. Our findings suggest that LINE-1 hypomethylation is an early event and Alu hypomethylation is probably a late event during breast cancer progression, and prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be related to chromosomal instability of this specific subtype.
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