Sensitive detection of hydroxymethylcytosine levels in normal and neoplastic cells and tissues

Annette M. Krais, Yoon Jung Park, Guido Reifenberger, Michael Meister, Christoph Plass, Heinz H. Schmeiser

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

A new sensitive analytical method using capillary electrophoresis with laser induced fluorescence (CE-LIF) was applied for the simultaneous detection of DNA methylation and hydroxymethylation levels in human cancers of different origin. DNA hydroxymethylation, measured as 5-hydroxymethylcytosine (5hmC) levels, was decreased in gliomas with mutation in the isocitrate dehydrogenase 1 (IDH1) gene when compared to IDH1-wildtype gliomas. Independent from IDH1 mutation, 5hmC levels were decreased in lung carcinomas when compared to normal lung tissue. Reduced DNA hydroxymethylation was also observed upon dedifferentiation in cultured murine embryonic fibroblasts. Our data show that reduced DNA hydroxymethylation is related to cellular dedifferentiation and can be detected in various types of cancers, independent from the IDH1 mutation status. Quantitative determination of altered 5hmC levels may therefore have potential as a biomarker linked to cellular differentiation and tumorigenesis.

Original languageEnglish
Pages (from-to)1293-1297
Number of pages5
JournalElectrophoresis
Volume40
Issue number9
DOIs
StatePublished - May 2019

Bibliographical note

Funding Information:
The investigated glioma tissue samples were retrieved from the tissue archive of the Institute of Neuropathology, Heinrich Heine University D?sseldorf, and analysed with approval by the institutional review board of the Medical Faculty, Heinrich Heine University D?sseldorf (study number 3532). DNAs from tumor and matched normal lung tissues with Non-Small Cell Lung Cancer (NSCLC) were kindly provided by the Lung Biobank Heidelberg, a member of the accredited Tissue Bank of the National Centre for Tumour Diseases (NCT) Heidelberg, the BioMaterialBank Heidelberg and the Biobank Platform of the German Centre for Lung Research (DZL). Written informed consent was obtained from all participants and/or their legal guardian/s before the use of the tissue for research purpose. The study was approved by the local Ethics Committee of the University of Heidelberg (no. 270/2001) and all experiments were performed in accordance with relevant guidelines and regulations.

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • Capillary electrophoresis with laser-induced fluorescence
  • DNA hydroxymethylation
  • Glioma
  • Hydroxymethylcytosine
  • Lung cancer

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