Mutator pathways unleashed by epigenetic silencing in human cancer.
Human cancers exhibit genomic instability and an increased mutation rate due to underlying defects in DNA repair genes. Hypermethylation of CpG islands in gene promoter regions is an important mechanism of gene inactivation in cancer. Many cellular pathways, including DNA repair, are inactivated by this type of epigenetic lesion, resulting in mutator pathways. In this review, we discuss the adverse consequences suffered by a cell when DNA repair genes such as the DNA mismatch repair gene hMLH1, the DNA alkyl-repair gene O(6)-methylguanine-DNA methyltransferase, the familial breast cancer gene BRCA1 and the Werner syndrome gene WRN become epigenetically silenced in human cancer.
Jacinto
Filipe V
FV
Cancer Epigenetics Laboratory, Molecular Pathology Programme, Spanish National Cancer Centre (CNIO), Madrid, Spain.
Esteller
Manel
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001483:Base Sequence; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D005090:Exodeoxyribonucleases; D005260:Female; D020868:Gene Silencing; D019398:Genes, BRCA1; D006801:Humans; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D053484:RecQ Helicases / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000071657:Werner Syndrome Helicase
D048868:Adaptor Proteins, Signal Transducing; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D005090:Exodeoxyribonucleases; D000070957:MutL Protein Homolog 1; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D045643:DNA Repair Enzymes