Journal Article

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

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

2021

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: ANP32E / Binding sites / Bioinformatics / Biomarkers, Tumor - analysis / Biomarkers, Tumor - metabolism / Biomedical and Life Sciences / Biomedicine / Breast - pathology / Breast Cancer / Breast Neoplasms - diagnosis / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Cancer Research / Carcinogenesis / Cell Line, Tumor / Chromatin / Chromatin - metabolism / Chromatin Immunoprecipitation Sequencing / Computer applications / Datasets / Datasets as Topic / Development and progression / Diagnosis / Disease Progression / Epigenetics / Female / FOXA1 / Gene expression / Gene Expression Regulation, Neoplastic / Genomes / Genomics / Health aspects / Health Promotion and Disease Prevention / Hepatocyte Nuclear Factor 3-alpha - metabolism / Histones / Humans / Immune response / Medicine/Public Health / Molecular chaperones / Molecular Chaperones - analysis / Molecular Chaperones - metabolism / Oncology / Ontology / Phenotypes / Physiological aspects / Research Article / Sox9 protein / Surgical Oncology / Transcription factors / Tumors