CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future.
We have come a long way since the first reports of the existence of aberrant DNA methylation in human cancer. Hypermethylation of CpG islands located in the promoter regions of tumor suppressor genes is now firmly established as an important mechanism for gene inactivation. CpG island hypermethylation has been described in almost every tumor type. Many cellular pathways are inactivated by this type of epigenetic lesion: DNA repair (hMLH1, MGMT), cell cycle (p16(INK4a), p15(INK4b), p14(ARF)), apoptosis (DAPK), cell adherence (CDH1, CDH13), detoxification (GSTP1), etc em leader However, we still know little of the mechanisms of aberrant methylation and why certain genes are selected over others. Hypermethylation is not an isolated layer of epigenetic control, but is linked to the other pieces of the puzzle such as methyl-binding proteins, DNA methyltransferases and histone deacetylase, but our understanding of the degree of specificity of these epigenetic layers in the silencing of specific tumor suppressor genes remains incomplete. The explosion of user-friendly technologies has given rise to a rapidly increasing list of hypermethylated genes. Careful functional and genetic studies are necessary to determine which hypermethylation events are truly relevant for human tumorigenesis. The development of CpG island hypermethylation profiles for every form of human tumors has yielded valuable pilot clinical data in monitoring and treating cancer patients based in our knowledge of DNA methylation. Basic and translational will both be needed in the near future to fully understand the mechanisms, roles and uses of CpG island hypermethylation in human cancer. The expectations are high.
Esteller
Manel
M
Cancer Epigenetics Laboratory, Molecular Pathology Program, Centro Nacional de Investigaciones Oncologicas, 28029 Madrid, Spain.
D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic
D005819:Genetic Markers