ArticleJCO precision oncology2024
5-Hydroxymethylcytosine Profiling of Cell-Free DNA Identifies Bivalent Genes That Are Prognostic of Survival in High-Risk Neuroblastoma.
Article in JCO precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Epigenetic Liquid Biopsy Enables Universal Mutation-Agnostic Molecular Surveillance for High-Risk Neuroblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- 5-hydroxymethylcytosine deposition mediates Polycomb repressive complex 2 function iniScience · 2026Article
- 5-hydroxymethylcytosine profiles in circulating cell-free DNA associate with disease status in patients with osteosarcoma.NPJ precision oncology · 2026Article
- 5-hydroxymethylcytosine profiles in circulating cell-free DNA associate with disease status in patients with osteosarcoma.Research square · 2025Article
- 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation.Biomarker research · 2025Review
- Characterizing Relationships between T-cell Inflammation and Outcomes in Patients with High-Risk Neuroblastoma According to Mesenchymal and Adrenergic Signatures.Cancer research communications · 2024Article
- Review
- Small-molecule inhibition of the METTL3/METTL14 complex suppresses neuroblastoma tumor growth and promotes differentiation.Cell reports · 2024Article
- 5-Hydroxymethylcytosine signals in serum are a predictor of chemoresistance in high-grade serous ovarian cancer.Gynecologic oncology · 2024Article
- Bivalent chromatin: a developmental balancing act tipped in cancer.Biochemical Society transactions · 2024Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
purposeNeuroblastoma is the most common extracranial solid tumor in childhood. We previously showed that circulating cell-free DNA (cfDNA) and tumor biopsy derived 5-hydroxymethylcytosime (5-hmC) profiles identified patients with neuroblastoma who experienced subsequent relapse. Here, we hypothesized that 5-hmC modifications selectively enriched in cfDNA compared with tumor biopsy samples would identify epigenetic changes associated with aggressive tumor behavior and identify novel biomarkers of outcome in patients with high-risk neuroblastoma.
methods5-hmC profiles from cfDNA (n = 64) and tumor biopsies (n = 48) were compared. Two neuroblastoma cell lines underwent chromatin immunoprecipitation followed by sequencing (ChIP-Seq) for H3K27me3, H3K4me3, and H3K27ac; kethoxal-associated single-stranded DNA sequencing; hmC-Seal for 5-hmC; and RNA-sequencing (RNA-Seq). Genes enriched for both H3K27me3 and H3K4me3 in the included cell lines were defined as bivalent. Using bivalent genes defined in vitro, a bivalent signature was established in three publicly available cohorts of patients with neuroblastoma through gene set variation analysis. Differences between tumors with high or low bivalent signatures were assessed by the Kaplan-Meier method and Cox proportional hazards models.
resultsIn cfDNA compared with tumor biopsy derived 5-hmC profiles, we found increased 5-hmC deposition on Polycomb Repressive Complex 2 target genes, a finding previously described in the context of bivalent genes. We identified 313 genes that bore bivalent chromatin marks, were enriched for mediators of neuronal differentiation, and were transcriptionally repressed across a panel of heterogeneous neuroblastoma cell lines. In three distinct clinical cohorts, low bivalent signature was significantly and independently associated with worse clinical outcome in patients with high-risk neuroblastoma.
conclusionLow expression of bivalent genes is a biomarker of worse outcome in patients with high-risk neuroblastoma.
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