title: DNA methylation, imprinting and cancer.
abstract: It is well known that a variety of genetic changes influence the development and progression of cancer. These changes may result from inherited or spontaneous mutations that are not corrected by repair mechanisms prior to DNA replication. It is increasingly clear that so called epigenetic effects that do not affect the primary sequence of the genome also play an important role in tumorigenesis. This was supported initially by observations that cancer genomes undergo changes in their methylation state and that control of parental allele-specific methylation and expression of imprinted loci is lost in several cancers. Many loci acquiring aberrant methylation in cancers have since been identified and shown to be silenced by DNA methylation. In many cases, this mechanism of silencing inactivates tumour suppressors as effectively as frank mutation and is one of the cancer-predisposing hits described in Knudson's two hit hypothesis. In contrast to mutations which are essentially irreversible, methylation changes are reversible, raising the possibility of developing therapeutics based on restoring the normal methylation state to cancer-associated genes. Development of such therapeutics will require identifying loci undergoing methylation changes in cancer, understanding how their methylation influences tumorigenesis and identifying the mechanisms regulating the methylation state of the genome. The purpose of this review is to summarise what is known about these issues.
authors.affiliation: Division of Human Cancer Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA. plass-1@medctr.osu.edu
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.forename: Paul D
authors.initials: PD
authors.lastname: Soloway
mesh_terms: D018899:CpG Islands / Q000235:genetics / Q000502:physiology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004273:DNA, Neoplasm