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Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma

Multiple myeloma (MM) and its precursors monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) are 2–3 times more common in African Americans (AA) than European Americans (EA). Although epigenetic changes are well recognized in the context of myeloma cell biology, th...

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Autores principales: Chiu, Brian C.-H., Zhang, Zhou, Derman, Benjamin A., Karpus, Jason, Luo, Liangzhi, Zhang, Sheng, Langerman, Spencer S., Sukhanova, Madina, Bhatti, Parveen, Jakubowiak, Andrzej, He, Chuan, Zhang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380317/
https://www.ncbi.nlm.nih.gov/pubmed/35974364
http://dx.doi.org/10.1186/s13045-022-01327-y
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author Chiu, Brian C.-H.
Zhang, Zhou
Derman, Benjamin A.
Karpus, Jason
Luo, Liangzhi
Zhang, Sheng
Langerman, Spencer S.
Sukhanova, Madina
Bhatti, Parveen
Jakubowiak, Andrzej
He, Chuan
Zhang, Wei
author_facet Chiu, Brian C.-H.
Zhang, Zhou
Derman, Benjamin A.
Karpus, Jason
Luo, Liangzhi
Zhang, Sheng
Langerman, Spencer S.
Sukhanova, Madina
Bhatti, Parveen
Jakubowiak, Andrzej
He, Chuan
Zhang, Wei
author_sort Chiu, Brian C.-H.
collection PubMed
description Multiple myeloma (MM) and its precursors monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) are 2–3 times more common in African Americans (AA) than European Americans (EA). Although epigenetic changes are well recognized in the context of myeloma cell biology, the contribution of 5-hydroxymethylcytosines (5hmC) to racial disparities in MM is unknown. Using the 5hmC-Seal and next-generation sequencing, we profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 342 newly diagnosed patients with MM (n = 294), SMM (n = 18), and MGUS (n = 30). We compared differential 5hmC modifications between MM and its precursors among 227 EA and 115 AA patients. The captured 5hmC modifications in cfDNA were found to be enriched in B-cell and T-cell-derived histone modifications marking enhancers. Of the top 500 gene bodies with differential 5hmC levels between MM and SMM/MGUS, the majority (94.8%) were distinct between EA and AA and enriched with population-specific pathways, including amino acid metabolism in AA and mainly cancer-related signaling pathways in EA. These findings improved our understanding of the epigenetic contribution to racial disparities in MM and suggest epigenetic pathways that could be exploited as novel preventive strategies in high-risk populations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-022-01327-y.
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spelling pubmed-93803172022-08-17 Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma Chiu, Brian C.-H. Zhang, Zhou Derman, Benjamin A. Karpus, Jason Luo, Liangzhi Zhang, Sheng Langerman, Spencer S. Sukhanova, Madina Bhatti, Parveen Jakubowiak, Andrzej He, Chuan Zhang, Wei J Hematol Oncol Correspondence Multiple myeloma (MM) and its precursors monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) are 2–3 times more common in African Americans (AA) than European Americans (EA). Although epigenetic changes are well recognized in the context of myeloma cell biology, the contribution of 5-hydroxymethylcytosines (5hmC) to racial disparities in MM is unknown. Using the 5hmC-Seal and next-generation sequencing, we profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 342 newly diagnosed patients with MM (n = 294), SMM (n = 18), and MGUS (n = 30). We compared differential 5hmC modifications between MM and its precursors among 227 EA and 115 AA patients. The captured 5hmC modifications in cfDNA were found to be enriched in B-cell and T-cell-derived histone modifications marking enhancers. Of the top 500 gene bodies with differential 5hmC levels between MM and SMM/MGUS, the majority (94.8%) were distinct between EA and AA and enriched with population-specific pathways, including amino acid metabolism in AA and mainly cancer-related signaling pathways in EA. These findings improved our understanding of the epigenetic contribution to racial disparities in MM and suggest epigenetic pathways that could be exploited as novel preventive strategies in high-risk populations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-022-01327-y. BioMed Central 2022-08-16 /pmc/articles/PMC9380317/ /pubmed/35974364 http://dx.doi.org/10.1186/s13045-022-01327-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Correspondence
Chiu, Brian C.-H.
Zhang, Zhou
Derman, Benjamin A.
Karpus, Jason
Luo, Liangzhi
Zhang, Sheng
Langerman, Spencer S.
Sukhanova, Madina
Bhatti, Parveen
Jakubowiak, Andrzej
He, Chuan
Zhang, Wei
Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma
title Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma
title_full Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma
title_fullStr Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma
title_full_unstemmed Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma
title_short Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma
title_sort genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free dna reveals population-specific pathways in the development of multiple myeloma
topic Correspondence
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380317/
https://www.ncbi.nlm.nih.gov/pubmed/35974364
http://dx.doi.org/10.1186/s13045-022-01327-y
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