DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women
INTRODUCTION: Incidence of estrogen receptor (ER)-negative breast cancer, an aggressive tumor subtype associated with worse prognosis, is higher among African American/Black women than other US racial and ethnic groups. The reasons for this disparity remain poorly understood but may be partially exp...
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ftpubmed:oai:pubmedcentral.nih.gov:10244512 2023-07-02T03:32:05+02:00 DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women Chen, Jianhong Higgins, Michael J. Hu, Qiang Khoury, Thaer Liu, Song Ambrosone, Christine B. Gong, Zhihong 2023-05-24 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244512/ https://doi.org/10.3389/fonc.2023.1167815 en eng Frontiers Media S.A. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244512/ http://dx.doi.org/10.3389/fonc.2023.1167815 Copyright © 2023 Chen, Higgins, Hu, Khoury, Liu, Ambrosone and Gong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Front Oncol Oncology Text 2023 ftpubmed https://doi.org/10.3389/fonc.2023.1167815 2023-06-11T01:00:49Z INTRODUCTION: Incidence of estrogen receptor (ER)-negative breast cancer, an aggressive tumor subtype associated with worse prognosis, is higher among African American/Black women than other US racial and ethnic groups. The reasons for this disparity remain poorly understood but may be partially explained by differences in the epigenetic landscape. METHODS: We previously conducted genome-wide DNA methylation profiling of ER- breast tumors from Black and White women and identified a large number of differentially methylated loci (DML) by race. Our initial analysis focused on DML mapping to protein-coding genes. In this study, motivated by increasing appreciation for the biological importance of the non-protein coding genome, we focused on 96 DMLs mapping to intergenic and noncoding RNA regions, using paired Illumina Infinium Human Methylation 450K array and RNA-seq data to assess the relationship between CpG methylation and RNA expression of genes located up to 1Mb away from the CpG site. RESULTS: Twenty-three (23) DMLs were significantly correlated with the expression of 36 genes (FDR<0.05), with some DMLs associated with the expression of single gene and others associated with more than one gene. One DML (cg20401567), hypermethylated in ER- tumors from Black versus White women, mapped to a putative enhancer/super-enhancer element located 1.3 Kb downstream of HOXB2. Increased methylation at this CpG correlated with decreased expression of HOXB2 (Rho=-0.74, FDR<0.001) and other HOXB/HOXB-AS genes. Analysis of an independent set of 207 ER- breast cancers from TCGA similarly confirmed hypermethylation at cg20401567 and reduced HOXB2 expression in tumors from Black versus White women (Rho=-0.75, FDR<0.001). DISCUSSION: Our findings indicate that epigenetic differences in ER- tumors between Black and White women are linked to altered gene expression and may hold functional significance in breast cancer pathogenesis. Text DML PubMed Central (PMC) Rho ENVELOPE(-63.000,-63.000,-64.300,-64.300) Frontiers in Oncology 13 |
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Oncology Chen, Jianhong Higgins, Michael J. Hu, Qiang Khoury, Thaer Liu, Song Ambrosone, Christine B. Gong, Zhihong DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women |
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Oncology |
description |
INTRODUCTION: Incidence of estrogen receptor (ER)-negative breast cancer, an aggressive tumor subtype associated with worse prognosis, is higher among African American/Black women than other US racial and ethnic groups. The reasons for this disparity remain poorly understood but may be partially explained by differences in the epigenetic landscape. METHODS: We previously conducted genome-wide DNA methylation profiling of ER- breast tumors from Black and White women and identified a large number of differentially methylated loci (DML) by race. Our initial analysis focused on DML mapping to protein-coding genes. In this study, motivated by increasing appreciation for the biological importance of the non-protein coding genome, we focused on 96 DMLs mapping to intergenic and noncoding RNA regions, using paired Illumina Infinium Human Methylation 450K array and RNA-seq data to assess the relationship between CpG methylation and RNA expression of genes located up to 1Mb away from the CpG site. RESULTS: Twenty-three (23) DMLs were significantly correlated with the expression of 36 genes (FDR<0.05), with some DMLs associated with the expression of single gene and others associated with more than one gene. One DML (cg20401567), hypermethylated in ER- tumors from Black versus White women, mapped to a putative enhancer/super-enhancer element located 1.3 Kb downstream of HOXB2. Increased methylation at this CpG correlated with decreased expression of HOXB2 (Rho=-0.74, FDR<0.001) and other HOXB/HOXB-AS genes. Analysis of an independent set of 207 ER- breast cancers from TCGA similarly confirmed hypermethylation at cg20401567 and reduced HOXB2 expression in tumors from Black versus White women (Rho=-0.75, FDR<0.001). DISCUSSION: Our findings indicate that epigenetic differences in ER- tumors between Black and White women are linked to altered gene expression and may hold functional significance in breast cancer pathogenesis. |
format |
Text |
author |
Chen, Jianhong Higgins, Michael J. Hu, Qiang Khoury, Thaer Liu, Song Ambrosone, Christine B. Gong, Zhihong |
author_facet |
Chen, Jianhong Higgins, Michael J. Hu, Qiang Khoury, Thaer Liu, Song Ambrosone, Christine B. Gong, Zhihong |
author_sort |
Chen, Jianhong |
title |
DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women |
title_short |
DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women |
title_full |
DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women |
title_fullStr |
DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women |
title_full_unstemmed |
DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women |
title_sort |
dna methylation differences in noncoding regions in er negative breast tumors between black and white women |
publisher |
Frontiers Media S.A. |
publishDate |
2023 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244512/ https://doi.org/10.3389/fonc.2023.1167815 |
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ENVELOPE(-63.000,-63.000,-64.300,-64.300) |
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Rho |
genre |
DML |
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DML |
op_source |
Front Oncol |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244512/ http://dx.doi.org/10.3389/fonc.2023.1167815 |
op_rights |
Copyright © 2023 Chen, Higgins, Hu, Khoury, Liu, Ambrosone and Gong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
op_doi |
https://doi.org/10.3389/fonc.2023.1167815 |
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Frontiers in Oncology |
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13 |
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