Inference of transcription factor binding from cell-free DNA enables tumor subtype prediction and early detection.
Nat Commun
; 10(1): 4666, 2019 10 11.
Article
em En
| MEDLINE
| ID: mdl-31604930
ABSTRACT
Deregulation of transcription factors (TFs) is an important driver of tumorigenesis, but non-invasive assays for assessing transcription factor activity are lacking. Here we develop and validate a minimally invasive method for assessing TF activity based on cell-free DNA sequencing and nucleosome footprint analysis. We analyze whole genome sequencing data for >1,000 cell-free DNA samples from cancer patients and healthy controls using a bioinformatics pipeline developed by us that infers accessibility of TF binding sites from cell-free DNA fragmentation patterns. We observe patient-specific as well as tumor-specific patterns, including accurate prediction of tumor subtypes in prostate cancer, with important clinical implications for the management of patients. Furthermore, we show that cell-free DNA TF profiling is capable of detection of early-stage colorectal carcinomas. Our approach for mapping tumor-specific transcription factor binding in vivo based on blood samples makes a key part of the noncoding genome amenable to clinical analysis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Fatores de Transcrição
/
Neoplasias da Mama
/
Neoplasias do Colo
/
Ácidos Nucleicos Livres
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article