University of Oulu

Taira, A., Palin, K., Kuosmanen, A. et al. Vitamin C boosts DNA demethylation in TET2 germline mutation carriers. Clin Epigenet 15, 7 (2023).

Vitamin C boosts DNA demethylation in TET2 germline mutation carriers

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Author: Taira, Aurora1,2; Palin, Kimmo1,2,3; Kuosmanen, Anna1,2;
Organizations: 1Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland
2Applied Tumor Genomics Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland
3iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland
4Department of Clinical Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
5Cancer Center, Kuopio University Hospital, Kuopio, Finland
6PEDEGO Research Unit, University of Oulu, Oulu, Finland
7Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
8Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4 MB)
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Language: English
Published: Springer Nature, 2023
Publish Date: 2023-08-09


Background: Accurate regulation of DNA methylation is necessary for normal cells to differentiate, develop and function. TET2 catalyzes stepwise DNA demethylation in hematopoietic cells. Mutations in the TET2 gene predispose to hematological malignancies by causing DNA methylation overload and aberrant epigenomic landscape. Studies on mice and cell lines show that the function of TET2 is boosted by vitamin C. Thus, by strengthening the demethylation activity of TET2, vitamin C could play a role in the prevention of hematological malignancies in individuals with TET2 dysfunction. We recently identified a family with lymphoma predisposition where a heterozygous truncating germline mutation in TET2 segregated with nodular lymphocyte-predominant Hodgkin lymphoma. The mutation carriers displayed a hypermethylation pattern that was absent in the family members without the mutation.

Methods: In a clinical trial of 1 year, we investigated the effects of oral 1 g/day vitamin C supplementation on DNA methylation by analyzing genome-wide DNA methylation and gene expression patterns from the family members.

Results: We show that vitamin C reinforces the DNA demethylation cascade, reduces the proportion of hypermethylated loci and diminishes gene expression differences between TET2 mutation carriers and control individuals.

Conclusions: These results suggest that vitamin C supplementation increases DNA methylation turnover and provide a basis for further work to examine the potential benefits of vitamin C supplementation in individuals with germline and somatic TET2 mutations.

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Series: Clinical epigenetics
ISSN: 1868-7075
ISSN-E: 1868-7083
ISSN-L: 1868-7075
Volume: 15
Issue: 1
Article number: 7
DOI: 10.1186/s13148-022-01404-6
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This study was supported by The Academy of Finland through the Finnish Center of Excellence in Tumor Genetics (312041, 335823), iCAN Digital Precision Cancer Medicine Flagship (320185) and an Academy Professorship (319083, 320149, Lauri Aaltonen) and grants from the University of Helsinki; Doctoral Programme in Biomedicine (Aurora Taira), The Emil Aaltonen foundation (Aurora Taira), Biomedicum Helsinki Foundation (Aurora Taira), Orion Research Foundation sr (Aurora Taira) and Ida Montin foundation (Aurora Taira).
Copyright information: © The Author(s) 2023. 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 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 The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.