TY - JOUR
T1 - Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma
AU - Chiu, Brian C.H.
AU - Chen, Chang
AU - You, Qiancheng
AU - Chiu, Rudyard
AU - Venkataraman, Girish
AU - Zeng, Chang
AU - Zhang, Zhou
AU - Cui, Xiaolong
AU - Smith, Sonali M.
AU - He, Chuan
AU - Zhang, Wei
N1 - Funding Information:
This work was supported in part by National Institutes of Health grants R21MD011439 (B.C.-H.C. and W.Z.), R01CA223662 (B.C.-H.C. and W.Z.), and UL1TR002389 (B.C.-H.C.). The authors would like to thank the Epidemiology and Research Recruitment Core of the University of Chicago Comprehensive Cancer Center for coordinating the subject recruitment and sample collection. C.H. is a Howard Hughes Medical Institute Investigator.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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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U2 - 10.1038/s41525-021-00179-8
DO - 10.1038/s41525-021-00179-8
M3 - Article
C2 - 33574286
AN - SCOPUS:85101148242
SN - 2056-7944
VL - 6
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 11
ER -