Genetic Medicine at University Hospital Essen
Cancer researchers are searching intensively for markers enabling doctors to detect malignant diseases at an early stage in order to increase the patients chances of recovery. During a research collaboration with the Institute for Pathology and Neuropathology, the Division of Haematology, the Institute for Medical Informatics, Biometry and Epidemiology and the Division of Urology, it was shown that carriers of a specific genotype (TT-genotype) of the GNAS locus experience a significant better course of various types of cancer than do carriers of the CC type (T393C-polymorphism). This phenomenon is found in cancer of the bladder, kidney, and large intestine and in one form of blood cancer (chronic lymphatic leukemia). On the basis of these research results, it will be possible to develop a simple genetic test for widespread use to detect many types of cancer at an early stage.
Children born after assisted reproduction, e. g. after in vitro fertilization (IVF), have a higher risk of low birth weight, deformities and certain genetic disorders. It is highly probable that epigenetic changes play a role here. Epigenetics describes the transmission of properties which do not involve changes in the underlying DNA sequences but rather inherited changes in gene regulation and gene expression. Together with the Endocrinology Centre in Hamburg, researchers at University Hospital Essen recently demonstrated that decreased fertility is itself associated with a higher risk of imprinting errors and that the risk is additionally increased by ovarian stimulation. In a new DFG-funded project scientists are now looking into the question of whether children who were procreated by sperm injection (ICSI) and have a low birth weight have an epimutation (inaccurate methylation pattern) in one parent-specific imprinted gene that is involved in the control of foetal growth. Since epigenetic changes could also be an important cause instead of a consequence of artificial insemination, researchers will be exploring the question of whether specific genetic sequences which encode for key proteins involved in epigenetic processes (e.g. DNA transferase and histone methyltransferase) are found more often in subfertile individuals.
#Genetically restructured, so-called recombinant monoclonal antibodies have dramatically improved the therapeutic possibilities for combating malignant diseases in the last 10 years.
The design, construction and production of custom-made recombinant antibodies with new effector functions can contribute to the development of immune therapies for malignant diseases. For this purpose, tumour-associated binding antigens, internalized antibodies and derived antibody fragments are selectively genetically manipulated in such a way that they are tolerated by the human immune system and also meet the necessary criteria (i.e. selectivity, sufficient affinity and biophysical stability) for successful clinical application. The selectivity and effectiveness of these antibodies are tested in animal models: later their potency is verified in clinical studies.
Pharmacogenetic markers are being investigated with a view to being able, with the help of genetic tests, to better predict the effectiveness of pharmaceuticals and the incidence of adverse reactions.
