دورية أكاديمية
DNA methylation and gene expression as determinants of genome-wide cell-free DNA fragmentation.
| العنوان: | DNA methylation and gene expression as determinants of genome-wide cell-free DNA fragmentation. |
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| المؤلفون: | Noë M; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Netherlands Cancer Institute, Amsterdam, The Netherlands., Mathios D; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Annapragada AV; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Koul S; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Foda ZH; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Medina JE; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Cristiano S; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Cherry C; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Bruhm DC; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Niknafs N; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Adleff V; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Ferreira L; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Easwaran H; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Baylin S; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Phallen J; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Scharpf RB; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. rscharpf@jhu.edu., Velculescu VE; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. velculescu@jhmi.edu. |
| المصدر: | Nature communications [Nat Commun] 2024 Aug 06; Vol. 15 (1), pp. 6690. Date of Electronic Publication: 2024 Aug 06. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
| مواضيع طبية MeSH: | DNA Methylation* , Cell-Free Nucleic Acids*/genetics , Cell-Free Nucleic Acids*/blood , DNA Fragmentation* , CpG Islands*/genetics , Neoplasms*/genetics, Humans ; Animals ; Mice ; Epigenesis, Genetic ; Female ; Isocitrate Dehydrogenase/genetics ; Male ; Gene Expression Regulation, Neoplastic |
| مستخلص: | Circulating cell-free DNA (cfDNA) is emerging as an avenue for cancer detection, but the characteristics of cfDNA fragmentation in the blood are poorly understood. We evaluate the effect of DNA methylation and gene expression on genome-wide cfDNA fragmentation through analysis of 969 individuals. cfDNA fragment ends more frequently contained CCs or CGs, and fragments ending with CGs or CCGs are enriched or depleted, respectively, at methylated CpG positions. Higher levels and larger sizes of cfDNA fragments are associated with CpG methylation and reduced gene expression. These effects are validated in mice with isogenic tumors with or without the mutant IDH1, and are associated with genome-wide changes in cfDNA fragmentation in patients with cancer. Tumor-related hypomethylation and increased gene expression are associated with decrease in cfDNA fragment size that may explain smaller cfDNA fragments in human cancers. These results provide a connection between epigenetic changes and cfDNA fragmentation with implications for disease detection. (© 2024. The Author(s).) |
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| معلومات مُعتمدة: | T32 GM136577 United States GM NIGMS NIH HHS; U01 CA271896 United States CA NCI NIH HHS; R01 CA121113 United States CA NCI NIH HHS; UG1 CA233259 United States CA NCI NIH HHS; P50 CA062924 United States CA NCI NIH HHS; P30 CA006973 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Cell-Free Nucleic Acids) EC 1.1.1.41 (Isocitrate Dehydrogenase) EC 1.1.1.42. (IDH1 protein, human) |
| تواريخ الأحداث: | Date Created: 20240806 Date Completed: 20240806 Latest Revision: 20240809 |
| رمز التحديث: | 20240812 |
| مُعرف محوري في PubMed: | PMC11303779 |
| DOI: | 10.1038/s41467-024-50850-8 |
| PMID: | 39107309 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2041-1723 |
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| DOI: | 10.1038/s41467-024-50850-8 |