5-Hydroxymethylcytosine Profiles in Circulating Cell-Free DNA Associate with Disease Burden in Children with Neuroblastoma.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 03 2020
15 03 2020
Historique:
received:
14
09
2019
revised:
05
11
2019
accepted:
12
12
2019
pubmed:
20
12
2019
medline:
15
1
2021
entrez:
20
12
2019
Statut:
ppublish
Résumé
5-Hydroxymethylcytosine (5-hmC) is an epigenetic marker of open chromatin and active gene expression. We profiled 5-hmC with Nano-hmC-Seal technology using 10 ng of plasma-derived cell-free DNA (cfDNA) in blood samples from patients with neuroblastoma to determine its utility as a biomarker. For the Discovery cohort, 100 5-hmC profiles were generated from 34 well children and 32 patients (27 high-risk, 2 intermediate-risk, and 3 low-risk) at various time points during the course of their disease. An independent Validation cohort encompassed 5-hmC cfDNA profiles ( Hierarchical clustering using 5-hmC levels of 347 genes identified from the Discovery cohort defined four clusters of samples that were confirmed in the Validation cohort and corresponded to high, high-moderate, moderate, and low/no metastatic burden. Samples from patients with increased metastatic burden had increased 5-hmC deposition on genes in neuronal stem cell maintenance and epigenetic regulatory pathways. Further, 5-hmC cfDNA profiles generated with 1,242 neuronal pathway genes were associated with subsequent relapse in the cluster of patients with predominantly low or no metastatic burden (sensitivity 65%, specificity 75.6%). cfDNA 5-hmC profiles in children with neuroblastoma correlate with metastatic burden and warrants development as a biomarker of treatment response and outcome.
Identifiants
pubmed: 31852832
pii: 1078-0432.CCR-19-2829
doi: 10.1158/1078-0432.CCR-19-2829
pmc: PMC7073281
mid: NIHMS1546969
doi:
Substances chimiques
Biomarkers, Tumor
0
Cell-Free Nucleic Acids
0
5-hydroxymethylcytosine
1123-95-1
5-Methylcytosine
6R795CQT4H
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1309-1317Subventions
Organisme : NCI NIH HHS
ID : K08 CA226237
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014599
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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