ArticlePediatric blood & cancer2024
Adrenergic and mesenchymal signatures are identifiable in cell-free DNA and correlate with metastatic disease burden in children with neuroblastoma.
Article in Pediatric blood & cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Alternative Splicing of the NF-Y Subunit, NF-YA, in Neuroblastoma Phenotype Heterogeneity.Cancers · 2026Review
- 5-hydroxymethylcytosine profiles in circulating cell-free DNA associate with disease status in patients with osteosarcoma.NPJ precision oncology · 2026Article
- Copy-Number Aberrations in Circulating Tumor DNA Enable Diagnosis and Risk Stratification of Pediatric Neuroblastic Tumors.Cancer research communications · 2026Article
- High-risk neuroblastoma as a model for immunotherapy of non-immunogenic cancers: where might we be in 20 years?Journal for immunotherapy of cancer · 2025Review
- 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
- A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations.Nature communications · 2024Article
- Review of Patient Gene Profiles Obtained through a Non-Negative Matrix Factorization-Based Framework to Determine the Role Inflammation Plays in Neuroblastoma Pathogenesis.International journal of molecular sciences · 2024Article
- 5-Hydroxymethylcytosine Profiling of Cell-Free DNA Identifies Bivalent Genes That Are Prognostic of Survival in High-Risk Neuroblastoma.JCO precision oncology · 2024Article
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10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCell-free DNA (cfDNA) profiles of 5-hydroxymethylcytosine (5-hmC), an epigenetic marker of open chromatin and active gene expression, are correlated with metastatic disease burden in patients with neuroblastoma. Neuroblastoma tumors are comprised of adrenergic (ADRN) and mesenchymal (MES) cells, and the relative abundance of each in tumor biopsies has prognostic implications. We hypothesized that ADRN and MES-specific signatures could be quantified in cfDNA 5-hmC profiles and would augment the detection of metastatic burden in patients with neuroblastoma.
methodsWe previously performed an integrative analysis to identify ADRN and MES-specific genes (n = 373 and n = 159, respectively). Purified DNA from cell lines was serial diluted with healthy donor cfDNA. Using Gene Set Variation Analysis (GSVA), ADRN and MES signatures were optimized. We then quantified signature scores, and our prior neuroblastoma signature, in cfDNA from 84 samples from 46 high-risk patients including 21 patients with serial samples.
resultsSamples from patients with higher metastatic burden had increased GSVA scores for both ADRN and MES gene signatures (p < .001). While ADRN and MES signature scores tracked together in serially collected samples, we identified instances of patients with increases in either MES or ADRN score at relapse.
conclusionsWhile it is feasible to identify ADRN and MES signatures using 5-hmC profiles of cfDNA from neuroblastoma patients and correlate these signatures to metastatic burden, additional data are needed to determine the optimal strategies for clinical implementation. Prospective evaluation in larger cohorts is ongoing.
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