Unraveling breast cancer heterogeneity through transcriptomic and epigenomic analysis

Breast cancer diversity is histologically evident as various proliferative benign lesions, in situ carcinomas, and invasive carcinomas that may develop into distant metastases. Breast tumor molecular subtypes have been defined by genome-wide expression microarray technology and reveal associations between genetic alterations and the malignant phenotype. Early work has been conducted to use subtype-specific biomarkers to elucidate targeted treatment options early in the course of breast cancer progression. Additionally, DNA methylation is an epigenetic modification that contributes to breast cancer progression by transcriptionally silencing certain tumor suppressor genes. Among the genes characterized as targets for silencing are well-established tumor suppressors such as RASSF1A, RARB, SFN, and TGM2. Measuring elevated gene copy number and aberrant gene promoter methylation can further facilitate characterization of breast tumor molecular subtype; however, profiling of breast tumors based on epigenetic criteria has yet to be established. Epigenomic analysis has been investigated for clinical applicability, and it has great promise when used in combination with minimally invasive techniques for both diagnostic and prognostic purposes.