Chromatin Variants Reveal the Genetic Determinants of Oncogenesis in Breast Cancer

Breast cancer presents as multiple distinct disease entities. Each tumor harbors diverse cell populations defining a phenotypic heterogeneity that impinges on our ability to treat patients. To date, efforts mainly focused on genetic variants to find drivers of inter- and intratumor phenotypic heterogeneity. However, these efforts have failed to fully capture the genetic basis of breast cancer. Through recent technological and analytical approaches, the genetic basis of phenotypes can now be decoded by characterizing chromatin variants. These variants correspond to polymorphisms in chromatin states at DNA sequences that serve a distinct role across cell populations. Here, we review the function and causes of chromatin variants as they relate to breast cancer inter- and intratumor heterogeneity and how they can guide the development of treatment alternatives to fulfill the goal of precision cancer medicine.