Super-enhancers (SEs) are large clusters of enhancers that drive specific expression programs that define cellular identity 8. They are characterized by histone modifications such as acetylation of histone H3 at lysine 27 (H3K27ac) and binding of coactivators such as p300 7. For example, cryptic promoters with modified histone marks were identified to drive gastric malignancy 6.Įnhancers are noncoding regions of the genome that harbor cis-regulatory elements and promote transcription of a target gene. Alteration of these epigenomic marks has been shown to play important roles in the development of different diseases including cancers. Gene expression alteration could also be caused by cis-element changes in noncoding genomic regions where transcription factors (TFs) or other regulators bind to 4, 5. It can be due to genetic changes such as copy numbers, chromosomal rearrangement, and somatic mutations of protein-coding genes. Transcriptome reprogramming is one of the critical features of cancer, where aberrant oncogene or tumor suppressor expression contributes to tumor initiation, progression, and metastasis.
On the other hand, the knowledge of deregulation of breast cancer epigenome in different subtypes that leads to various phenotypic outcomes remains poorly understood. However, the lack of common genetic alternations in TNBC has limited the development of targeted therapies for this malignancy. Key genomic alterations associated with different subtypes of breast cancer, including PTEN, PIK3CA, HER2, BRCA, and TP53, have been comprehensively characterized. Chemotherapy, usually with high toxicity, is the main treatment option for triple-negative breast cancer (TNBC), thus underscoring the clinical need for identifying novel therapeutic targets for this aggressive subtype. The majority of basal-like tumors (~70%) are triple-negative (ER-/PR-/HER2-) 2, 3.
Molecular studies based on gene expression profiles have revealed different breast cancer subtypes: luminal, HER2+/ER−, and basal like. Breast cancer is the most common cancer and the leading cause of cancer death among women worldwide 1.