Chromatin reorganisation and differential transcription factor binding in breast cancer

Breast cancer (BRC) is a heterogenous disease defined by complex gene regulatory profiles manifested by differential transcription factor (TF) binding. Both genetic and epigenetic changes contribute towards the development and metastasis of the disease. Our study focuses on chromatin changes in areas of specific interest such as transcription factor binding sites (TFBSs). Using nucleosome positioning maps determined experimentally in paired normal/tumour breast tissues and cell-free DNA (cfDNA) from blood plasma, we set to determine deregulated TF binding and to narrow down a subset of TFBSs which have biomarker potential for breast cancer diagnostics. We used multiple methods, including defining genomic regions with consistently changed nucleosome patterns in BRC. Then we defined TFBSs enriched in these regions and calculated nucleosome repositioning at subsets of cancer sensitive TFBSs defined using our novel method. Several TFs showed promising biomarker characteristics in this analysis, with Estrogen Receptor (ER) being the most prominent example. Our study demonstrates the potential to stratify patients based on blood plasma cfDNA using nucleosomics analysis. This provides new arguments for the use of nucleosome repositioning as a possible diagnosis tool in liquid biopsies.