Chromatin Organization and Transcriptional Programming of Breast Cancer Cell Identity.

The advent of sequencing technologies for assessing chromosome conformations has provided a wealth of information on the organization of the 3-dimensional genome and its role in cancer progression. It is now known that changes in chromatin folding and accessibility can promote aberrant activation or repression of transcriptional programs that can drive tumorigenesis and progression in diverse cancers. This includes breast cancer, which comprises several distinct subtypes defined by their unique transcriptomes that dictate treatment response and patient outcomes. Of these, basal-like breast cancer is an aggressive subtype controlled by a pluripotency-enforcing transcriptome. Meanwhile, the more differentiated luminal subtype of breast cancer is driven by an estrogen receptor-dominated transcriptome that underlies its responsiveness to antihormone therapies and conveys improved patient outcomes. Despite the clear differences in molecular signatures, the genesis of each subtype from normal mammary epithelial cells remains unclear. Recent technical advances have revealed key distinctions in chromatin folding and organization between subtypes that could underlie their transcriptomic and, hence, phenotypic differences. These studies also suggest that proteins controlling particular chromatin states may be useful targets for treating aggressive disease. In this review, we explore the current state of understanding of chromatin architecture in breast cancer subtypes and its potential role in defining their phenotypic characteristics. © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Jessica R Bobbitt, Darcie D Seachrist, Ruth A Keri. Chromatin Organization and Transcriptional Programming of Breast Cancer Cell Identity. Endocrinology. 2023 Jun 26;164(8)

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PMID: 37394919

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