DNA methylation and mRNA expression at early and late stage of breast cancer as well as pre-malignant neoplasia

Due to improved disease diagnostics, most of the operated breast tumours today are T1/T2 and the distinction between them is of great importance for prognosis. The categorization and distinction between T1 and T2 can be a matter of millimetres, but is of significant importance for the patient in terms of further decisions of treatment. It is therefore of enormous clinical importance to be able to identify molecular signatures separating between T1 and T2. Both mRNA and array CGH as well as methylation ca n provide quantitative markers of progression, which do not call for categorization and error associated with threshold decisions. With this appliaction we will attempt to add miRNA expression as well as aCGH and methylation analysis to the information fr om mRNA expression for a more refined clinical marker profile of T2 tumors that may add more biological clues to the pathways and gene regulation networks underlying tumour progression. Since we already observe a signal at mRNA level, there is a good cha nce to refine these observations by studying upstream regulatory mechanisms at methylation (this proposal) and miRNA levels (other ongoing). Deep sequencing analysis will inevitably provide insights not detectable by conventional array based methods.