Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma

The 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome...

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Autores principales: Chiu, Brian C.-H., Chen, Chang, You, Qiancheng, Chiu, Rudyard, Venkataraman, Girish, Zeng, Chang, Zhang, Zhou, Cui, Xiaolong, Smith, Sonali M., He, Chuan, Zhang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878492/
https://www.ncbi.nlm.nih.gov/pubmed/33574286
http://dx.doi.org/10.1038/s41525-021-00179-8
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author Chiu, Brian C.-H.
Chen, Chang
You, Qiancheng
Chiu, Rudyard
Venkataraman, Girish
Zeng, Chang
Zhang, Zhou
Cui, Xiaolong
Smith, Sonali M.
He, Chuan
Zhang, Wei
author_facet Chiu, Brian C.-H.
Chen, Chang
You, Qiancheng
Chiu, Rudyard
Venkataraman, Girish
Zeng, Chang
Zhang, Zhou
Cui, Xiaolong
Smith, Sonali M.
He, Chuan
Zhang, Wei
author_sort Chiu, Brian C.-H.
collection PubMed
description The 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach.
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spelling pubmed-78784922021-02-24 Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma Chiu, Brian C.-H. Chen, Chang You, Qiancheng Chiu, Rudyard Venkataraman, Girish Zeng, Chang Zhang, Zhou Cui, Xiaolong Smith, Sonali M. He, Chuan Zhang, Wei NPJ Genom Med Article The 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach. Nature Publishing Group UK 2021-02-11 /pmc/articles/PMC7878492/ /pubmed/33574286 http://dx.doi.org/10.1038/s41525-021-00179-8 Text en © The Author(s) 2021 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chiu, Brian C.-H.
Chen, Chang
You, Qiancheng
Chiu, Rudyard
Venkataraman, Girish
Zeng, Chang
Zhang, Zhou
Cui, Xiaolong
Smith, Sonali M.
He, Chuan
Zhang, Wei
Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma
title Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma
title_full Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma
title_fullStr Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma
title_full_unstemmed Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma
title_short Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma
title_sort alterations of 5-hydroxymethylation in circulating cell-free dna reflect molecular distinctions of subtypes of non-hodgkin lymphoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878492/
https://www.ncbi.nlm.nih.gov/pubmed/33574286
http://dx.doi.org/10.1038/s41525-021-00179-8
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