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

Abstract 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 profil...

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Autores principales:	Brian C.-H. Chiu, Chang Chen, Qiancheng You, Rudyard Chiu, Girish Venkataraman, Chang Zeng, Zhou Zhang, Xiaolong Cui, Sonali M. Smith, Chuan He, Wei Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/c07415f9cf8248ff98fd82fcb6e0f829
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spelling	oai:doaj.org-article:c07415f9cf8248ff98fd82fcb6e0f8292021-12-02T14:11:35ZAlterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma10.1038/s41525-021-00179-82056-7944https://doaj.org/article/c07415f9cf8248ff98fd82fcb6e0f8292021-02-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00179-8https://doaj.org/toc/2056-7944Abstract 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.Brian C.-H. ChiuChang ChenQiancheng YouRudyard ChiuGirish VenkataramanChang ZengZhou ZhangXiaolong CuiSonali M. SmithChuan HeWei ZhangNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Brian C.-H. Chiu Chang Chen Qiancheng You Rudyard Chiu Girish Venkataraman Chang Zeng Zhou Zhang Xiaolong Cui Sonali M. Smith Chuan He Wei Zhang Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma
description	Abstract 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.
format	article
author	Brian C.-H. Chiu Chang Chen Qiancheng You Rudyard Chiu Girish Venkataraman Chang Zeng Zhou Zhang Xiaolong Cui Sonali M. Smith Chuan He Wei Zhang
author_facet	Brian C.-H. Chiu Chang Chen Qiancheng You Rudyard Chiu Girish Venkataraman Chang Zeng Zhou Zhang Xiaolong Cui Sonali M. Smith Chuan He Wei Zhang
author_sort	Brian C.-H. Chiu
title	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_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_sort	alterations of 5-hydroxymethylation in circulating cell-free dna reflect molecular distinctions of subtypes of non-hodgkin lymphoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c07415f9cf8248ff98fd82fcb6e0f829
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Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma

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