Transcription factor-nucleosome dynamics from plasma cfDNA identifies ER-driven states in breast cancer.

ABSTRACT: Genome-wide binding profiles of estrogen receptor (ER) and FOXA1 reflect cancer state in ER⁺ breast cancer. However, routine profiling of tumor transcription factor (TF) binding is impractical in the clinic. Here, we show that plasma cell-free DNA (cfDNA) contains high-resolution ER and FOXA1 tumor binding profiles for breast cancer. Enrichment of TF footprints in plasma reflects the binding strength of the TF in originating tissue. We defined pure in vivo tumor TF signatures in plasma using ER⁺ breast cancer xenografts, which can distinguish xenografts with distinct ER states. Furthermore, state-specific ER-binding signatures can partition human breast tumors into groups with significantly different ER expression and mortality. Last, TF footprints in human plasma sam

SUBMITTER: Rao S 

PROVIDER: S-EPMC9401618 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature