Disappearance of genetic material can tumor cells to grow

Universitätsmedizin Berlin, Max Delbrück Centre for Molecular Medicine (MDC) Berlin-Buch, the Max-Planck-Institut für Genetik Berlin-and four other German institutions followed a specific gene loss in a certain human Lymphoma, the emergence of hitherto largely unexplained is to prove. They examined the so-called Sézary syndrome. This is an aggressive cancer of disease from the Group of primary skin lymphomas, the so-called "primary cutaneous lymphomas." The results of the study, published in the current issue of the journal of experimental medicine *, offer fundamental new insights into the history and development of Sézary syndrome and possibly other human lymphomas as well.

Malignant Sézary syndrome is characterized by the reproduction of a special kind of white blood cells in the skin of male and female patients. In contrast with most other skin lymphomas manifesto patients with Sézary's syndrome not only infection of the skin, but also contamination of blood and lymph nodes by degenerate t cells even at the beginning of the disease. The researchers examined highly purified tumor cells of patients with Sézary syndrome using modern, high resolution genetic procedures (called array comparative genomic hybridization technique) of hitherto unknown genetic changes. It identified areas in the genotype of this tumor cells that may have been lost in many of the patients studied. A detailed analysis of these areas showed that one of the most often gene codes for a so-called transcription factor influenced. Transcription factors have important functions in the regulation of cellular gene activity.

"The partial loss of the gene for E2A transcription factor seems to be a very crucial role to play in this context because the gene normally is of great importance for natural lymphocyte development," explains Chalid Assaf of the Charité Klinik für Dermatologie und Venerologie Allergology. In mice leads to a loss of this gene to the emergence of aggressive t cell lymphomas. However, a gene loss in one of the different classes of human Lymphoma had not yet been found so far.

The researchers also identified various E2A-regulated genes and signal paths in tumor cells, the pure deregulation of each of which would be sufficient to produce a tumor to develop. "Loss of E2A in Sézary syndrome is of crucial importance for the aggressive behavior of the tumor cells because it contributes to a faster, uncontrolled growth of cells," stresses Stephan Matha, a scientist at the Charité Klinik für Hämatologie und Onkologie and MDC. Consequently, it was directly for the first time that E2A in humans the function of a tumor suppressor. The researchers hope that these findings may in the future possibly forms the basis for the development of new concepts for treatment of patients with Sézary syndrome new and more effective therapies.

Sources: Universitätsmedizin Berlin, AlphaGalileo Foundation.