Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid

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, MR.
Inference of transcription factor binding from cell-free DNA enables tumor subtype prediction and early detection.
Nat Commun. 2019; 10(1): 4666-4666. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bauernhofer Thomas
Belic Jelena
Geigl Jochen Bernd
Gerger Armin
Heitzer Ellen
Lazzeri Isaac
Moser Tina
Perakis Samantha
Petru Edgar
Schimek Michael G.
Sill Heinz
Speicher Michael
Ulz Peter
Wölfler Albert
Zebisch Armin
Zhou Qing
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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.

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