Entwicklung von Oligonukleotid-Arrays für die Charakterisierung von genomischen DNA-Methylierungsmustern in Tumoren

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Changes in genomic DNA methylation patterns are one of the earliest and most consistent features of tumourigenesis. However, very little is known about the nature of these changes and their role in cellular transformation. Progress in the field has been hampered by the unavailability of methods for genomic epigenetic profiling. Using chronic lymphocytic leukemia as a model system, we have shown previously that aberrant DNA methylation profiles can be used as a valuable marker for clinical tumour characterisation. In independent experiments, we have established a method for the detection of single-base polymorphisms on oligonucleotide microarrays. Because the methylation status of a defined nucleotide can also be interpreted to represent a single nucleotide polymorphism, we propose to utilise the latter technology for a genome-wide, gene-specific analysis of DNA methylation patterns. This approach will result in a detailed characterisation of genomic methylation patterns. The data will be evaluated together with the available clinical data and results from trancriptional profiling. Our results will allow fundamental insights into the role of DNA methylation during tumouresis and will provide the foundation for an epigenetic classification of tumours.