UNTERSUCHUNGEN ZUR MOLEKULAREN PATHOGENESE VON FOLLIKULÄREN SCHILDDRÜSENTUMOREN

Thyroid tumors belong to the most frequent epithelial tumors. On the basis of their histologically and clinically definable forms and stages they represent an outstanding model system for tumorgenesis. Cytogenetic analyses can serve here as an excellent and efficient tool for cloning tumor-relevant genes. Known important cytogenetic changes in adenomas are trisomy 7 as well as breaks in chromosomal bands 19q13.4 and 2p21. Starting from these data, in the present work the breakpoint cluster 19q13.4 was cloned. The newly found upstream lying zinc finger gene ZNF331 was described as a candidate-gene. The second relevant breakpoint cluster in band 2p21 was cloned as well. Here the newly found candidate gene THADA was described which fuses through translocations to different other chromosomes, creating a truncated fusion protein. It could clearly be shown that the HMGA2 gene has an influence on the tumor progression of epithelial thyroid gland cells. Since in animal tissues HMGA2, as shown in mice, is only active during the embryonal stages, the issue arises whether an observed overexpression evokes a tumorigenic status and therefore might be a suitable central point of application for a therapy