Epigenetic mechanisms in the development of malignant lymphoma

During the past years epigenetic changes have been increasingly recognised as an important mechanism for altered gene expression in malignant cells, and they have been suggested to be even more common than genetic changes in human cancer. Epigenetics include mechanisms that influence expression of a gene without permanently changing the DNA, and the most studied mechanism is transcriptional inactivation of tumor-suppressor genes due to hypermethylation of promoter regions. Altered DNA methylation patterns may serve as biomarkers for cancer detection, assessment of prognosis, and prediction of response to therapy. Importantly, this is also of therapeutic interest, as methylation is potentially reversible with demethylating agents.

In this project we want to identify methylated genes in lymphomas by comparing data from several lymphoma cell lines and primary biopsies. Changes in methylation status after treatment with demethylation agents will be assayed by microarry studies and correlated to gene expression profiling data from lymphoma subtypes. Our aim is to identify marker genes for early lymphoma development and for the different subtypes of lymphomas in order to start early a suitable treatment and to detect minimal residual disease.