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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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Volume 50, Issue 10


Global DNA hypomethylation in cancer: review of validated methods and clinical significance

Estela G. Toraño
  • Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain
  • Estela G. Toraño and Sandra Petrus contributed equally to this review.
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sandra Petrus
  • Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain
  • Estela G. Toraño and Sandra Petrus contributed equally to this review.
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Agustin F. Fernandez
  • Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mario F. Fraga
  • Corresponding author
  • Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain
  • Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2012-07-15 | DOI: https://doi.org/10.1515/cclm-2011-0902


DNA methylation is one of the best-known epigenetic modifications in mammals. The alteration of DNA methylation patterns has been found to be related to many diseases, including cancer. It is well-known that during carcinogenesis, a site-specific DNA hypermethylation and a global DNA hypomethylation take place. This overall loss of DNA methylation has been proposed as a valid biomarker for cancer. Given its medical utility, in recent years it has become apparent that there is a need to develop methods for the analysis of DNA methylation using different approaches: global, locus-specific, or genome-wide. Here we review some of these techniques and discuss their potential clinical utility.

Keywords: biomarkers; cancer; DNA methylation; hypomethylation

About the article

Estela G. Toraño

Estela G. Toraño is a first year PhD student in Cancer Epigenetics under the supervision of Dr. Mario F. Fraga. She has a fellowship from FICYT (Fundación para el fomento en Asturias de la investigación científica aplicada y la tecnología). Before she began her phD, she graduated in Biology and enrolled a master in cancer research at the University of Oviedo. Her work is focused on changes in post-translational modifications of histones during cellular differentiation and tumorigenesis. Also, she works in the study of methylomes of cancer and is familiar with the methods to analyze DNA methylation.

Sandra Petrus

Originally from Menorca (Spain), graduated in Biotechnology and currently Biomedical Sciences master student (Cancer Genomics and Developmental Biology Programme) at the University of Utrecht (The Netherlands). Relevant research experience in genetic epidemiology of bladder cancer, epigenetics in monozygotic twins and developmental biology of blood endothelial cells in zebrafish. Awarded with a Summer-Training fellowship by the Spanish National Cancer Research Centre (CNIO) in 2010 and with a Collaboration grant from the Spanish Ministry of Education and Science (MEC) in 2010–2011.

Agustin F. Fernandez

Agustin F. Fernandez is, at present, a Miguel Servet researcher at the University Institute of Oncology of Asturias (IUOPA) where he works in the Cancer Epigenetics laboratory located at the Asturias Central University Hospital (HUCA), Oviedo, Spain. He received his PhD in Genetics from the University of Oviedo, and worked as postdoctoral fellow in the Laboratory of Cancer Epigenetics at the Spanish National Cancer Research Centre (CNIO), Madrid, Spain, and, later, at the Bellvitge Institute for Biomedical Research (IDIBELL), Barcelona, Spain. His main research areas are in the field of epigenetics and comprise the epigenetic mechanisms involved in cell differentiation, and their alterations in aging and different pathologies including cancer.

Mario F. Fraga

Mario F. Fraga is a Tenured Scientist at the National Centre of Biotechnology (CNB-CSIC) and the Head of the Cancer Epigenetics Laboratory at the Institute of Oncology of Asturias (IUOPA), Spain. He received his PhD in plant epigenetics from the University of Oviedo, and was a “Ramon y Cajal” postdoctoral fellow at the Spanish National Cancer Research Centre (CNIO), where he focused his research on cancer epigenetics and the study of human interindividual epigenetic variation. The research interests of his team are epigenetic processes involved in cell differentiation and their alterations in cancer and aging.

Corresponding author: Mario F. Fraga, Centro Nacional de Biotecnología (CNB-CSIC), Darwin, 3 Cantoblanco, 28049 Madrid, Spain Phone: +34 985 109 475

Received: 2011-12-05

Accepted: 2012-06-08

Published Online: 2012-07-15

Published in Print: 2012-10-01

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 50, Issue 10, Pages 1733–1742, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2011-0902.

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