ArticleNature communications2025
Pan-cancer multi-omic model of LINE-1 activity reveals locus heterogeneity of retrotransposition efficiency.
Article in Nature communications, 2025. 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 18 papers.
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Who cites it
18 citing papers in PubMed.
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Transposable Element Activation: A Hallmark of Cancer.Cancer discovery · 2026Review
- DICER1-related tumour predisposition mutations increase 3p-miRNA function and HERVH activity.Nature communications · 2026Article
- Multiomic profiling links L1 retrotransposition to genomic instability and ecDNA in bladder cancer.Nature communications · 2026Article
- Transcriptional Activation of Transposable Element (TE)-Associated Genes Is Frequently Associated with Altered Promoter Methylation in Placenta and Melanoma.International journal of molecular sciences · 2026Article
- LINE-1 retrotransposons: Multifaceted functions and regulatory mechanisms in health and disease.Molecular therapy. Nucleic acids · 2026Review
- The interferon-stimulated gene product HERC5 inhibits human LINE-1 retrotransposition with an ISGylation-independent mechanism.Nucleic acids research · 2026Article
- Targeting age-related LINE-1 activation alleviates cardiac aging.Nature aging · 2026Article
- Retroelements in thyroid cancer: epigenetic plasticity, dedifferentiation, and therapeutic opportunities.Reviews in endocrine & metabolic disorders · 2026Review
- Article
- Repeats mimic pathogen-associated patterns across a vast evolutionary landscape.Cell genomics · 2025Article
- Article
- Emerging hallmarks and the rise of complexities and heterogeneity of tumor.Biochemistry and biophysics reports · 2025Review
- Pan-cancer analysis reveals context-dependent roles of LINE-1 ORF1p in immune regulation and copy number alterations.bioRxiv : the preprint server for biology · 2025Article
- Multi-platform framework for mapping somatic retrotransposition in human tissues.bioRxiv : the preprint server for biology · 2025Article
- YRDC is a Prognostic-Related Biomarker Correlated With Immune Infiltration and Drug Sensitivity in Pan-Cancer.Cancer reports (Hoboken, N.J.) · 2025Article
- Bioenergetic Model of Retrotransposon Activity in Cancer Cells.Life (Basel, Switzerland) · 2025Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
16 authors.
Funding
Abstract
Somatic mobilization of LINE-1 (L1) has been implicated in cancer etiology. We analyzed a recent TCGA data release comprised of nearly 5000 pan-cancer paired tumor-normal whole-genome sequencing (WGS) samples and ~9000 tumor RNA samples. We developed TotalReCall an improved algorithm and pipeline for detection of L1 retrotransposition (RT), finding high correlation between L1 expression and "RT burden" per sample. Furthermore, we mathematically model the dual regulatory roles of p53, where mutations in TP53 disrupt regulation of both L1 expression and retrotransposition. We found those with Li-Fraumeni Syndrome (LFS) heritable TP53 pathogenic and likely pathogenic variants bear similarly high L1 activity compared to matched cancers from patients without LFS, suggesting this population be considered in attempts to target L1 therapeutically. Due to improved sensitivity, we detect over 10 genes beyond TP53 whose mutations correlate with L1, including ATRX, suggesting other, potentially targetable, mechanisms underlying L1 regulation in cancer remain to be discovered.
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