ArticleGenome medicine2012
Genomic vulnerability to LINE-1 hypomethylation is a potential determinant of the clinicogenetic features of multiple myeloma.
Article in Genome medicine, 2012. 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 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Pooled it
- Deciphering epigenetic crosstalk in multiple myeloma pathogenesis and treatment.Clinical epigenetics · 2026Review
- Decoding osteosarcoma from heterogeneity to precision therapy.Discover oncology · 2025Review
- Epigenetic modifications of the PHOX2A and CDH2 genes expression- new insights into the pathogenesis of multiple myeloma.BMC cancer · 2025Article
- CpG dinucleotide methylation of the SPDEF gene as a blood-based epigenetic biomarker for prostate cancer diagnosis.BMC urology · 2025Article
- Epigenetic Modeling of Jumping Translocations of 1q Heterochromatin in Acute Myeloid Leukemia After 5'-Azacytidine Treatment.Genes, chromosomes & cancer · 2024Article
- LINE-1 hypomethylation, increased retrotransposition and tumor-specific insertion in upper gastrointestinal cancer.Cancer science · 2024Article
- Review
- Increased Expression of SETDB1 Predicts Poor Prognosis in Multiple Myeloma.BioMed research international · 2022Article
- Review
- Combinatory low methylation statuses of SAT-α and L1 are associated with shortened survival time in patients with advanced gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2019Article
- Article
- The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response.Frontiers in oncology · 2018Review
- LINE-1 methylation level and prognosis in pancreas cancer: pyrosequencing technology and literature review.Surgery today · 2017Review
- Epigenetic Regulation of Centromere Chromatin Stability by Dietary and Environmental Factors.Advances in nutrition (Bethesda, Md.) · 2017Review
- Epigenetic regulatory mutations and epigenetic therapy for multiple myeloma.Current opinion in hematology · 2017Review
- Global, cancer-specific microRNA cluster hypomethylation was functionally associated with the development of non-B non-C hepatocellular carcinoma.Molecular cancer · 2016Article
- Article
- Clinical use and applications of histone deacetylase inhibitors in multiple myeloma.Clinical pharmacology : advances and applications · 2016Review
- Evidence of an epigenetic origin for high-risk 1q21 copy number aberrations in multiple myeloma.Blood · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe aim of this study was to clarify the role of global hypomethylation of repetitive elements in determining the genetic and clinical features of multiple myeloma (MM).
methodsWe assessed global methylation levels using four repetitive elements (long interspersed nuclear element-1 (LINE-1), Alu Ya5, Alu Yb8, and Satellite-α) in clinical samples comprising 74 MM samples and 11 benign control samples (7 cases of monoclonal gammopathy of undetermined significance (MGUS) and 4 samples of normal plasma cells (NPC)). We also evaluated copy-number alterations using array-based comparative genomic hybridization, and performed methyl-CpG binding domain sequencing (MBD-seq).
resultsGlobal levels of the repetitive-element methylation declined with the degree of malignancy of plasma cells (NPC>MGUS>MM), and there was a significant inverse correlation between the degree of genomic loss and the LINE-1 methylation levels. We identified 80 genomic loci as common breakpoints (CBPs) around commonly lost regions, which were significantly associated with increased LINE-1 densities. MBD-seq analysis revealed that average DNA-methylation levels at the CBP loci and relative methylation levels in regions with higher LINE-1 densities also declined during the development of MM. We confirmed that levels of methylation of the 5' untranslated region of respective LINE-1 loci correlated strongly with global LINE-1 methylation levels. Finally, there was a significant association between LINE-1 hypomethylation and poorer overall survival (hazard ratio 2.8, P = 0.015).
conclusionGlobal hypomethylation of LINE-1 is associated with the progression of and poorer prognosis for MM, possibly due to frequent copy-number loss.
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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.