Imagen de Portada

Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse

Guardado en:
Publicado en:PLoS One vol. 20, no. 7 (Jul 2025), p. e0327483
Autor principal: Fu, Ruiqing
Otros Autores: He, Amy Su, Zhao, Yi, Tian, Yafei, Chen, Hongyan, Lu, Daru
Publicado:
Public Library of Science
Materias:
Cancer
DNA methylation
Tumors
Plasma
Tumorigenesis
Fragments
Mutation
Cell culture
Variation
Deoxyribonucleic acid > DNA
Xenotransplantation
Tumor cell lines
Genomes
Animal models
DNA fragmentation
Fragmentation
Xenografts
Environmental
Acceso en línea:Citation/Abstract
Full Text
Full Text - PDF
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Resumen:Cell-free DNA (cfDNA) is increasingly studied for its diverse applications in non-invasive detection. Non-randomly cleaved by nucleases and released into the bloodstream, cfDNA exhibits a variety of intrinsic fragmentation patterns indicative of cell status. Particularly, these fragmentation patterns have recently been demonstrated to be effective in predicting cancer and its tissue-of-origin, owing to increased variation of fragmentation features observed in tumor patients. However, there remains a lack of detailed exploration of altered cfDNA fragmentation profiles in tumors, which consist of a mixture of both non-tumor cfDNA and circulating tumor DNA (ctDNA). Hence, we leveraged the human tumor cell line-derived xenograft (CDX) mouse model, where different tumor cell lines were implanted into different anatomical sites, to isolate pure ctDNA and separately investigate the fragment properties of CDX-cfDNA and ctDNA. We found an enrichment of short cfDNA fragments in both CDX-cfDNA and ctDNA compared to normal plasma cfDNA, with more elevated short fragments in ctDNA. Moreover, the CDX-cfDNA fragmentation features distinguished between CDX models of different tumor cell lines, while the ctDNA fragmentation features conversely discriminate between CDX models of different anatomical sites. The results suggested that both non-tumor cfDNA and ctDNA contribute to the increased variation observed in tumors, and that cfDNA fragmentation may be highly variable and susceptible to regulations by both original cells and cells within the local niche.
ISSN:1932-6203
DOI:10.1371/journal.pone.0327483
Fuente:Health & Medical Collection