Princess Margaret Cancer Centre, Toronto, Ontario M5G 1L7, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
Cold Spring Harb Perspect Med. 2022 Oct 3;12(10):a041322. doi: 10.1101/cshperspect.a041322.
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.
乳腺癌表现为多种不同的疾病实体。每个肿瘤都包含不同的细胞群体，这些群体定义了表型异质性，这影响了我们治疗患者的能力。迄今为止，研究主要集中在遗传变异上，以寻找肿瘤间和肿瘤内表型异质性的驱动因素。然而，这些努力未能完全捕捉到乳腺癌的遗传基础。通过最近的技术和分析方法，通过描述染色质变异，现在可以解码表型的遗传基础。这些变体对应于 DNA 序列上染色质状态的多态性，这些多态性在细胞群体中发挥着不同的作用。在这里，我们回顾了染色质变异的功能和原因，以及它们与乳腺癌肿瘤间和肿瘤内异质性的关系，以及它们如何指导治疗替代方案的开发，以实现精准癌症医学的目标。
