The Loss of Methyl Groups in DNA of Tumor Cells and Tissues

The Immunochemical Approach
  • Alain Niveleau
  • Chandrika Piyathilake
  • Adriana de Capoa
  • Claudio Grappelli
  • Jean-Marc Dumollard
  • Lucien Frappart
  • Emmanuel Drouet
Part of the Medical Intelligence Unit book series (MIUN)


The existence of 5-methyldeoxycytidine (5-MeCyd) has been first demonstrated in 1958. For several years the presence of this naturally modified base in DNA remained unexplained and its role was ignored until a relationship was established between the expression of ovalbumin and the methylation status of the gene coding for this protein in various tissues. The gene was not methylated in the oviduct whereas it was methylated in the brain where ovalbumin was not expressed. This first observation prompted numerous studies that investigated the distribution and the role of this modified base in genomic DNA. A further significant progress was accomplished when it was demonstrated that tumor genomes were globally less methylated than their normal counterparts. This important observation was made using DNA that had been extracted from tissue samples and then submitted to extensive digestion by nucleases and reverse phase high pressure liquid chromatography analysis. The development of gene-specific hybridization techniques together with the availability of an ever-increasing number of methylation-sensitive restriction enzymes allowed the methylation status of numerous genes to be investigated, especially DNA derived from tumors. This gene-specific analysis has revealed that in addition to genome-wide hypomethylation, local hypermethylated sites were identified in tumors in concert with an increased DNA methyltransferase activity. For several years most studies in the field-aimed at the detection of altered methylation patterns of oncogenes ^ or tumor suppressor genes.


Squamous Cell Carcinoma Methylation Status Epithelial Hyperplasia Global Hypomethylation Normal Bronchial Epithelial Cell 
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Copyright information

© and Kluwer Academic/Plenum Publishers 2005

Authors and Affiliations

  • Alain Niveleau
    • 1
  • Chandrika Piyathilake
    • 2
  • Adriana de Capoa
    • 3
  • Claudio Grappelli
    • 4
  • Jean-Marc Dumollard
    • 5
  • Lucien Frappart
    • 6
  • Emmanuel Drouet
    • 7
  1. 1.Laboratoire de Virologie Structurale et Moleculaire Faculte de MedecineUniversite Joseph Fourier de GrenobleLa TroncheFrance
  2. 2.Department of Nutrition Sciences Division of Nutritional Biochemistry and Molecular BiologyUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Dipartimento di Genetica e Biologia MolecolareUniversita di RomaRoamItaly
  4. 4.Dipartimento di Genetica e Biologia MolecolareUniversita di Roma 1 La SapienzaRomeItaly
  5. 5.Service d’Anatomie et de Cytologie PathologiquesHopital BellevueSaint-EtienneFrance
  6. 6.Unit INSERM 403Facult de M decine LaennecLyonFrance
  7. 7.Laboratoire de Virologie Moleculaire et Sturcturale Faculte de M decine et PharmacieUniversit Joseph Fourier de GrenobleLa TroncheFrance

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