DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women
IntroductionIncidence 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 expla...
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ftdoajarticles:oai:doaj.org/article:1ee7428404bd4b3ca385a79c10e729c8 2023-06-11T04:11:18+02:00 DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women Jianhong Chen Michael J. Higgins Qiang Hu Thaer Khoury Song Liu Christine B. Ambrosone Zhihong Gong 2023-05-01T00:00:00Z https://doi.org/10.3389/fonc.2023.1167815 https://doaj.org/article/1ee7428404bd4b3ca385a79c10e729c8 EN eng Frontiers Media S.A. https://www.frontiersin.org/articles/10.3389/fonc.2023.1167815/full https://doaj.org/toc/2234-943X 2234-943X doi:10.3389/fonc.2023.1167815 https://doaj.org/article/1ee7428404bd4b3ca385a79c10e729c8 Frontiers in Oncology, Vol 13 (2023) breast cancer DNA methylation noncoding regions ER negative tumor Black and White women Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 article 2023 ftdoajarticles https://doi.org/10.3389/fonc.2023.1167815 2023-05-28T00:36:47Z IntroductionIncidence 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.MethodsWe 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. ResultsTwenty-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).DiscussionOur 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. Article in Journal/Newspaper DML Directory of Open Access Journals: DOAJ Articles Rho ENVELOPE(-63.000,-63.000,-64.300,-64.300) Frontiers in Oncology 13 |
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breast cancer DNA methylation noncoding regions ER negative tumor Black and White women Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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breast cancer DNA methylation noncoding regions ER negative tumor Black and White women Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jianhong Chen Michael J. Higgins Qiang Hu Thaer Khoury Song Liu Christine B. Ambrosone Zhihong Gong DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women |
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breast cancer DNA methylation noncoding regions ER negative tumor Black and White women Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
description |
IntroductionIncidence 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.MethodsWe 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. ResultsTwenty-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).DiscussionOur 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 |
Article in Journal/Newspaper |
author |
Jianhong Chen Michael J. Higgins Qiang Hu Thaer Khoury Song Liu Christine B. Ambrosone Zhihong Gong |
author_facet |
Jianhong Chen Michael J. Higgins Qiang Hu Thaer Khoury Song Liu Christine B. Ambrosone Zhihong Gong |
author_sort |
Jianhong Chen |
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 |
https://doi.org/10.3389/fonc.2023.1167815 https://doaj.org/article/1ee7428404bd4b3ca385a79c10e729c8 |
long_lat |
ENVELOPE(-63.000,-63.000,-64.300,-64.300) |
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Rho |
geographic_facet |
Rho |
genre |
DML |
genre_facet |
DML |
op_source |
Frontiers in Oncology, Vol 13 (2023) |
op_relation |
https://www.frontiersin.org/articles/10.3389/fonc.2023.1167815/full https://doaj.org/toc/2234-943X 2234-943X doi:10.3389/fonc.2023.1167815 https://doaj.org/article/1ee7428404bd4b3ca385a79c10e729c8 |
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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