The use of Methylated DNA Immunoprecipitation MeDIP in cancer for better clinical management
Coordinator: Manel ESTELLER
Project Number: 200620
EC contribution: € 2,999,994.00
Project website: http://www.cancerdip.eu/
Aberrant DNA methylation is the most common molecular lesion of the cancer cell. Neither gene mutation nor cytogenetic abnormalities are as common in human tumours as DNA methylation alterations. The stability of our genome and correct gene expression is maintained to a great extent thanks to a perfectly preestablished pattern of DNA methylation and histone modifications. In cancer this idealistic scenario breaks down due to an interesting phenomenon whereby the regulatory regions (CpG islands) of certain tumour suppressor genes become hypermethylated, inactivating the gene as a consequence, whilst a wave of hypomethylation occurs in the genome. Indeed, CpG island promoter hypermethylation has a tumour-type-specific pattern, where each gene tends to be methylated in the cancer cells driven from a particular tissue, but not from others. It is also widely accepted that the multiprotein complex associated with the methylated DNA is also crucially involved in the repression of gene expression. Another aspect crucial for the interest of epigenetics in cancer is that promoter hypermethylation of the CpG island of tumours suppressor genes occurs early in tumorigenesis. Furthermore, it has been extensively reported that CpG promoter hypermethylation can be used as predictor of cancer behaviour and a predictor of response to treatment. This characteristic makes promoter hypermethylation combined with the epigenetic associated proteins profile, a potential biomarker for early detection of cancer and for the individualization of cancer treatment. We are going to use a novel technique based in chromatin immunoprecipitation, the Methylated DNA Immunoprecipitation (MeDIP) technique that will easily permit us to obtain an epigenomic profile which will be used to personalize cancer treatment and facilitate tumour diagnosis, prognosis and monitoring.