Lung Cancer pp 101-109 | Cite as

Sensitive Detection of Hypermethylated p16INK4a Alleles in Exfoliative Tissue Material

  • Marcus Schuermann
  • Michael Kersting
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 74)

Abstract

Epigenetic DNA modification by aberrant methylation of cytosine residues is thought to be an important mechanism contributing to tumorigenesis. Methylation of cytosines normally occurs at distinct sites of the genome containing stretches of repeated CpG (CpG islands) often found within promoter areas of transcribed genes. The cytosine methylation pattern is established very early in development by a continuous process of demethylation and de novo methylation (for review see refs. 1,2). Normally, methylation patterns are faithfully maintained through all subsequent cell divisions and are dependent on DNA methyltransferase activity (3). It has been observed, however, that tumour cells often show extensive upregulation of DNA methyltransferase and at the same time hypomethylation of CpG sites (4). The mechanism of this apparent deregulation in cancer cells is not clear but is generally thought that de novo methylation of otherwise nonmethylated genes is the active component of functional disturbance in cancer (4-6). Methylated islands will recruit special methyl-binding proteins and in conjunction with histone deacetylases are then thought to form repressive chromatin states around the promoter regions, leading to transcriptional loss of genes residing downstream (7). If important genes reside within this region loss of functional control in cell proliferation will ensue. It is therefore not surprising that de novo methylation found in cancer includes many tumor-suppressor genes known to date, thus forming an alternative to gene silencing by inactivating deletions (8).

Keywords

Estrogen EDTA Leukemia Agarose Bromide 

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Copyright information

© Humana Press Inc., Totowa, NJ 2003

Authors and Affiliations

  • Marcus Schuermann
    • 1
  • Michael Kersting
    • 2
  1. 1.Department of Hematology, Oncology,and ImmunologyPhilipps-University of MarburgMarburgGermany
  2. 2.GATC Biotech AGKonstanzGermany

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