Inference of tumor cell-specific transcription factor binding from cell-free DNA

Peter Ulz, Samantha Perakis, Qing Zhou, Tina Moser, Jelena Belic, Albert Wölfler, Armin Zebisch, Armin Gerger, Gunda Pristauz, Edgar Petru, Michael G. Schimek, Jochen B. Geigl, Thomas Bauernhofer, Heinz Sill, Christoph Bock, Ellen Heitzer, Michael R. Speicher

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Nov 06, 2018
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Received Date: 29th October 18

Alterations in transcription factors are important drivers of tumorigenesis, but non-invasive assays for assessing transcription factor activity are lacking. Here, we evaluated the feasibility of inferring transcription factor binding in solid tumors from their nucleosome footprint in circulating cell-free DNA. We developed a novel analysis pipeline to determine accessibility of transcription factor binding sites and applied it to 244 cell-free DNA samples from patients with prostate, breast and colon cancer. We observed patient-specific as well as tumor-specific patterns. Specifically, inferred binding patterns for the transcription factors AR, HOXB13, and NKX3-1 allowed us to classify patients by tumor type, including subtypes of prostate cancer, which has clinical implications for the management of patients. Our approach for mapping tumor-specific transcription factor binding in vivo based on blood samples makes a key part of the noncoding genome amenable for clinical analysis.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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