Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden.
Nat Commun
; 12(1): 2229, 2021 04 13.
Article
em En
| MEDLINE
| ID: mdl-33850132
ABSTRACT
Profiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we develop a quantitative method, exploiting local tissue-specific cell-free DNA (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent of genomic aberrations. Nucleosome-dependent cfDNA degradation at promoters and first exon-intron junctions is strongly associated with differential transcriptional activity in tumors and blood. A quantitative model, based on just 6 regulatory regions, could accurately predict ctDNA levels in colorectal cancer patients. Strikingly, a model restricted to blood-specific regulatory regions could predict ctDNA levels across both colorectal and breast cancer patients. Using compact targeted sequencing (<25 kb) of predictive regions, we demonstrate how the approach could enable quantitative low-cost tracking of ctDNA dynamics and disease progression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carga Tumoral
/
Fragmentação do DNA
/
Ácidos Nucleicos Livres
/
DNA Tumoral Circulante
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Singapura