title: Epigenetics provides a new generation of oncogenes and tumour-suppressor genes.
abstract: Cancer is nowadays recognised as a genetic and epigenetic disease. Much effort has been devoted in the last 30 years to the elucidation of the 'classical' oncogenes and tumour-suppressor genes involved in malignant cell transformation. However, since the acceptance that major disruption of DNA methylation, histone modification and chromatin compartments are a common hallmark of human cancer, epigenetics has come to the fore in cancer research. One piece is still missing from the story: are the epigenetic genes themselves driving forces on the road to tumorigenesis? We are in the early stages of finding the answer, and the data are beginning to appear: knockout mice defective in DNA methyltransferases, methyl-CpG-binding proteins and histone methyltransferases strongly affect the risk of cancer onset; somatic mutations, homozygous deletions and methylation-associated silencing of histone acetyltransferases, histone methyltransferases and chromatin remodelling factors are being found in human tumours; and the first cancer-prone families arising from germline mutations in epigenetic genes, such as hSNF5/INI1, have been described. Even more importantly, all these 'new' oncogenes and tumour-suppressor genes provide novel molecular targets for designed therapies, and the first DNA-demethylating agents and inhibitors of histone deacetylases are reaching the bedside of patients with haematological malignancies.
authors.affiliation: Cancer Epigenetics Laboratory, 3rd Floor, Molecular Pathology Programme, Spanish National Cancer Centre (CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain. mesteller@cnio.es
authors.forename: M
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002843:Chromatin; D019175:DNA Methylation; D015254:DNA Modification Methylases; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D006657:Histones; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009857:Oncogenes
chemical_list: D002843:Chromatin; D006657:Histones; D015254:DNA Modification Methylases