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

Ulz, P.; Perakis, S.; Zhou, Q.; Moser, T.; Belic, J.; Wölfler, A.; Zebisch, A.; Gerger, A.; Pristauz, G.; Petru, E.; Schimek, M. G.; Geigl, J. B.; Bauernhofer, T.; Sill, H.; Bock, C.; Heitzer, E.; Speicher, M. R.

doi:10.1101/456681

bioRxiv · 10.1101/456681

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

Ulz, P.·Perakis, S.·Zhou, Q.·Moser, T.·Belic, J.·Wölfler, A.·Zebisch, A.·Gerger, A.·Pristauz, G.·Petru, E.·Schimek, M. G.·Geigl, J. B.·Bauernhofer, T.·Sill, H.·Bock, C.·Heitzer, E.·Speicher, M. R.

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Abstract

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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Ulz, P., Perakis, S., Zhou, Q., Moser, T., Belic, J., Wölfler, A., Zebisch, A., Gerger, A., Pristauz, G., Petru, E., Schimek, M. G., Geigl, J. B., Bauernhofer, T., Sill, H., Bock, C., Heitzer, E., Speicher, M. R.. 2018-10-30. Inference of tumor cell-specific transcription factor binding from cell-free DNA. https://doi.org/10.1101/456681

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