DNA methylation as a prognostic and diagnostic biomarker for cancer
Epigenetic inactivation of tumor suppressor genes (TSG) plays a central role in the neoplastic transformation of somatic cells. Inactivation of TSG is accomplished through a repressive chromatin state and DNA hypermethylation of the respective gene promoter. Especially, de novo methylation of CpG island promoters is a hallmark of TSG silencing during malignant transformation. Hypermethylated promoters correlate with different patho-histological features including impaired survival and advanced tumor stage and represent novel diagnostic and prognostic biomarkers. Aberrant DNA methylation patterns are mainly maintained by the DNA methyltransferase 1 (DNMT1) and initiated by DNMT3A and DNMT3B. Inhibition of DNMT represents a novel target for cancer therapy.
In our previous work, we have characterized several genes which are often hypermethylated in cancers or during differentiation. Especially, we have identified the RASSF1A tumor suppressor, which is frequently epigenetically inactivated in human tumors. In further work, we will analyze in collaboration with investigator of the Medical Faculty the methylation profiles of distinct tumor entities. We will evaluate, if the methylation profile and genetic alteration correlates to a progression model and is associated with clinical and prognostic parameter. Furthermore, we will identify other cancer-related genes, which might be frequently hypermethylated in human cancer. Thus, methylation profiling may serve as diagnostic and prognostic markers.