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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Ulz P,Perakis S,Zhou Q,Moser T,Belic J,Lazzeri I,Wölfler A,Zebisch A,Gerger A,Pristauz G,Petru E,White B,Roberts CES,John JS,Schimek MG,Geigl JB,Bauernhofer T,Sill H,Bock C,Heitzer E,Speicher MRdoi
10.1038/s41467-019-12714-4subject
Has Abstractpub_date
2019-10-11 00:00:00pages
4666issue
1issn
2041-1723pii
10.1038/s41467-019-12714-4journal_volume
10pub_type
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