Molekularzytogenetische und molekulargenetische Untersuchungen an Schilddrüsentumoren

The focus of the present study was on the molecular-cytogenetic analysis of the main cytogenetic subgroups in follicular lesions of the thyroid. Quantitative molecular-cytogenetic analysis of benign thyroid lesions revealed that much greater importance is attached to the main cytogenetic subgroups, i.e. trisomy 7 and rearrangements of 2p21 or 19q13.4, than by conventional cytogenetic analysis alone. For 2p21-rearrangements it was possible to identify and to further characterize the target gene, THADA, involved in these rearrangements. Further analyses suggest that the truncation of THADA is in correlation with the proliferation of epithelial cells und the genesis of benign thyroid lesions. For 19q13.4 rearrangements the breakpoints were narrowed down to a region of about 150 kb which is in close proximity to two miRNA clusters, C19MC and mir-371-3, which both are activated as a result of the rearrangements. The molecular-cytogenetic analysis of benign as well as malign follicular thyroid neoplasias with respect to the translocation t(2;3)(q13;p25) and the PAX8/PPARγ fusion gene, respectively, revealed that this aberration occurs only in a small fraction of follicular adenomas. Molecular-cytogenetic characterization of the 3p25 breakpoint region reveals that rearrangements of the 3p25 region occur independently of the 2q13 region and the PAX8 gene, respectively. Thus this region is considered as a hot spot region in thyroid neoplasias with follicular origin. In conclusion the results of the present study point out the status of molecular cytogenetics with respect to the analysis of tumor-specific chromosomal aberrations in general and in particular to the relevance of these aberrations to the pathogenesis of benign follicular thyroid lesions.