The first high-resolution DNA promoter "methylome" in colorectal cancer tissue samples

• Antragsteller: Dr. Michael Wirtenberger
• Fachliche Zuordnung: Epidemiologie und Medizinische Biometrie/Statistik
• Förderung: Förderung von 2007 bis 2008
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 48595597

The prominent role of epigenetic alterations in colorectal cancer (CRC) is a well-known feature. Aberrant DNA methylation is the most common molecular defect in cancer cells. Promoter DNA hypermethylation leads to silencing of tumour suppressor genes, while DNA hypomethylation causes activation of oncogenes and loss of imprinting. Beside the reported epimutations involved in CRC, molecular evidence suggests additional aberrantly methylated genes. Thus, the specific aims of the proposed project are: a) The establishment of the first genome-wide high-resolution promoter DNA methylation pattern in CRC tissue samples to identify new and disease stage-specific epimutations, b) The definition of novel epigenetic markers for a better characterisation of CRC subtypes and their correlation with clinico-pathologic parameters, and c) The investigation of the functional association between the genomewide CpG island methylation pattern and the genome-wide expression profiles in CRC tissue samples. The identification of novel epimutations and their validation as epigenetic markers in the present project will be crucial for early diagnosis and treatment response control. Additionally, it will have important implications for the identification of factors that control and govern de novo CpG island methylation in CRC and the development of demethylating agents.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: Neuseeland
• Gastgeber: Professor Antony E. Reeve