Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma
Abstract 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 bi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13045-022-01327-y |
| _version_ | 1798038895882928128 |
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| author | Brian C.-H. Chiu Zhou Zhang Benjamin A. Derman Jason Karpus Liangzhi Luo Sheng Zhang Spencer S. Langerman Madina Sukhanova Parveen Bhatti Andrzej Jakubowiak Chuan He Wei Zhang |
| author_facet | Brian C.-H. Chiu Zhou Zhang Benjamin A. Derman Jason Karpus Liangzhi Luo Sheng Zhang Spencer S. Langerman Madina Sukhanova Parveen Bhatti Andrzej Jakubowiak Chuan He Wei Zhang |
| author_sort | Brian C.-H. Chiu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T21:46:36Z |
| format | Article |
| id | doaj.art-512264b742af4149b25c0f4a6d8b8862 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-11T21:46:36Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-512264b742af4149b25c0f4a6d8b88622022-12-22T04:01:23ZengBMCJournal of Hematology & Oncology1756-87222022-08-011511510.1186/s13045-022-01327-yGenome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myelomaBrian C.-H. Chiu0Zhou Zhang1Benjamin A. Derman2Jason Karpus3Liangzhi Luo4Sheng Zhang5Spencer S. Langerman6Madina Sukhanova7Parveen Bhatti8Andrzej Jakubowiak9Chuan He10Wei Zhang11Department of Public Health Sciences, The University of ChicagoDepartment of Preventive Medicine, Northwestern University Feinberg School of MedicineSection of Hematology/Oncology, Department of Medicine, The University of ChicagoDepartment of Chemistry, The University of ChicagoDepartment of Chemistry, The University of ChicagoDepartment of Chemistry, The University of ChicagoDepartment of Public Health Sciences, The University of ChicagoDepartment of Pathology, Northwestern University Feinberg School of MedicineDepartment of Cancer Control Research, BC Cancer Research InstituteSection of Hematology/Oncology, Department of Medicine, The University of ChicagoDepartment of Chemistry, The University of ChicagoDepartment of Preventive Medicine, Northwestern University Feinberg School of MedicineAbstract 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.https://doi.org/10.1186/s13045-022-01327-yMultiple myeloma5-hydroxymethylcytosineRacial disparityEpigenetic modification |
| spellingShingle | Brian C.-H. Chiu Zhou Zhang Benjamin A. Derman Jason Karpus Liangzhi Luo Sheng Zhang Spencer S. Langerman Madina Sukhanova Parveen Bhatti Andrzej Jakubowiak Chuan He Wei Zhang Genome-wide profiling of 5-hydroxymethylcytosines in circulating cell-free DNA reveals population-specific pathways in the development of multiple myeloma Journal of Hematology & Oncology Multiple myeloma 5-hydroxymethylcytosine Racial disparity Epigenetic modification |
| 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 | Multiple myeloma 5-hydroxymethylcytosine Racial disparity Epigenetic modification |
| url | https://doi.org/10.1186/s13045-022-01327-y |
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