| Added by | llasorsa |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Circulating nuclear DNA structural features, origins, and complete size profile revealed by fragmentomics |
| Creator | Sanchez et al. |
| Author | Cynthia Sanchez |
| Author | Thibault Mazard |
| Author | Philippe Blache |
| Author | Zahra Al Amir Dache |
| Author | Brice Pastor |
| Author | Ekaterina Pisareva |
| Author | Rita Tanos |
| Author | Alain R. Thierry |
| Abstract | To unequivocally address their unresolved intimate structures in blood, we scrutinized the size distribution of circulating cell-free DNA (cfDNA) using whole-genome sequencing (WGS) from both double- and single-strand DNA library preparations (DSP and SSP, n = 7) and using quantitative PCR (Q-PCR, n = 116). The size profile in healthy individuals was remarkably homogenous when using DSP sequencing or SSP sequencing. CfDNA size profile had a characteristic nucleosome fragmentation pattern. Overall, our data indicate that the proportion of cfDNA inserted in mono-nucleosomes, di-nucleosomes, and chromatin of higher molecular size (>1000 bp) can be estimated as 67.5% to 80%, 9.4% to 11.5%, and 8.5% to 21.0%, respectively. Although DNA on single chromatosomes or mono-nucleosomes is detectable, our data revealed that cfDNA is highly nicked (97%-98%) on those structures, which appear to be subjected to continuous nuclease activity in the bloodstream. Fragments analysis allows the distinction of cfDNA of different origins: first, cfDNA size profile analysis may be useful in cfDNA extract quality control; second, subtle but reliable differences between metastatic colorectal cancer patients and healthy individuals vary with the proportion of malignant cell-derived cfDNA in plasma extracts, pointing to a higher degree of cfDNA fragmentation and nuclease activity in samples with high malignant cell cfDNA content. |
| Publication | JCI insight |
| Volume | 6 |
| Issue | 7 |
| Pages | 144561 |
| Date | 2021-04-08 |
| Journal Abbr | JCI Insight |
| Language | eng |
| DOI | 10.1172/jci.insight.144561 |
| ISSN | 2379-3708 |
| Library Catalog | PubMed |
| Extra | PMID: 33571170 PMCID: PMC8119211 |
| Tags | Adult, Cell-Free Nucleic Acids, Colorectal Neoplasms, Diagnostics, DNA, DNA, Single-Stranded, Female, Humans, Male, Middle Aged, Oncology, Polymerase Chain Reaction, Whole Genome Sequencing |
| Date Added | 2022/09/29 - 15:21:59 |
| Date Modified | 2024/10/10 - 16:52:29 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
