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BMC Cancer
Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Breast Cancer | Research article

Subtype-Independent ANP32E Reduction During Breast Cancer Progression in Accordance with Chromatin Relaxation

Authors: Garrett L. Ruff, Kristin E. Murphy, Zachary R. Smith, Paula M. Vertino, Patrick J. Murphy

Published in: BMC Cancer | Issue 1/2021

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Abstract

Background

Chromatin state provides a clear decipherable blueprint for maintenance of transcriptional patterns, exemplifying a mitotically stable form of cellular programming in dividing cells. In this regard, genomic studies of chromatin states within cancerous tissues have the potential to uncover novel aspects of tumor biology and unique mechanisms associated with disease phenotypes and outcomes. The degree to which chromatin state differences occur in accordance with breast cancer features has not been established.

Methods

We applied a series of unsupervised computational methods to identify chromatin and molecular differences associated with discrete physiologies across human breast cancer tumors.

Results

Chromatin patterns alone are capable of stratifying tumors in association with cancer subtype and disease progression. Major differences occur at DNA motifs for the transcription factor FOXA1, in hormone receptor-positive tumors, and motifs for SOX9 in Basal-like tumors. We find that one potential driver of this effect, the histone chaperone ANP32E, is inversely correlated with tumor progression and relaxation of chromatin at FOXA1 binding sites. Tumors with high levels of ANP32E exhibit an immune response and proliferative gene expression signature, whereas tumors with low ANP32E levels appear programmed for differentiation.

Conclusions

Our results indicate that ANP32E may function through chromatin state regulation to control breast cancer differentiation and tumor plasticity. This study sets a precedent for future computational studies of chromatin changes in carcinogenesis.
Appendix
Available only for authorised users
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Metadata
Title
Subtype-Independent ANP32E Reduction During Breast Cancer Progression in Accordance with Chromatin Relaxation
Authors
Garrett L. Ruff
Kristin E. Murphy
Zachary R. Smith
Paula M. Vertino
Patrick J. Murphy
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-09077-9

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