Triple-negative breast cancer (TNBC) is a clinically challenging and molecularly heterogenous breast cancer subgroup. Here, we investigate t
Triple-negative breast cancer (TNBC) is a clinically challenging and molecularly heterogenous breast cancer subgroup. Here, we investigate the DNA methylation landscape of TNBC. By analyzing tumor methylome profiles and accounting for the genomic context of CpG methylation, we divide TNBC into two epigenetic subtypes corresponding to a Basal and a non-Basal group, in which characteristic transcriptional patterns are correlated with DNA methylation of distal regulatory elements and epigenetic regulation of key steroid response genes and developmental transcription factors. Further subdivision of the Basal and non-Basal subtypes identifies subgroups transcending genetic and proposed TNBC mRNA subtypes, demonstrating widely differing immunological microenvironments, putative epigenetically-mediated immune evasion strategies, and a specific metabolic gene network in older patients that may be epigenetically regulated. Our study attempts to target the epigenetic backbone of TNBC, an approach that may inform futurestudies regarding tumor origins and the role of the microenvironment in shaping the cancer epigenome.
Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Translational Cancer Research, Breast/lung cancer, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för translationell cancerforskning, Bröst/lungcancer, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breast/lungcancer, Research Group Lung Cancer, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröst/lungcancer, Forskningsgrupp Lungcancer, Originator, Lund University, Profile areas and other strong research environments, Other Strong Research Environments, LUCC: Lund University Cancer Centre, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Övriga starka forskningsmiljöer, LUCC: Lunds universitets cancercentrum, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Clinical Genetics, The genetics of soft tissue tumors, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för klinisk genetik, Genetiska avvikelser i mjukdelstumörer, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breast/ovarian cancer, Breast and Ovarian Cancer Genomics, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröst/ovarialcancer, Bröst- och ovarialcancer, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breastcancer-genetics, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröstcancer-genetik, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breastcancer-genetics, Familial Breast Cancer, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröstcancer-genetik, Familjär bröstcancer, Originator
