Vergleichende molekulargenetische Untersuchungen benigner mesenchymaler und maligner epithelialer Tumoren unter besonderer Berücksichtigung des Schilddrüsenkarzinoms
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Other Titles: | Comparative molecular genetic analyses of benign mesenchmymal and malignant epithelial tumours with emphasis on thyroid carcinomas | Authors: | Klemke, Markus | Supervisor: | Bullerdiek, Jörn | 1. Expert: | Bullerdiek, Jörn | Experts: | Dotzauer, Andreas | Abstract: | Although leiomyomas of the uterus are the most frequent gynecological tumours, their pathogenesis remains largely unknown. Chromosomal rearrangements affecting the region 12q14~15 belong to the most frequent recurrent chromosomal aberrations. A strong overexpression of HMGA2 in this group was confirmed in the present thesis. Since losses of miRNA binding sites due to truncated transcripts caused by intragenic breakpoints occur in a minority of these tumours, they cannot account for the reactivation of HMGA2 in leiomyomas of the 12q14~15 group in general. Moreover, fibroids without cytogenetically detectable 12q14~15 aberration were found to express HMGA2 at higher rates than the corresponding myometrium. Therefore, HMGA2 may also be of pathogenetic relevance in fibroids without chromosomal abnormalities and could possibly play a crucial role in a much larger fraction of uterine leiomyomas than previously assumed. Besides benign mesenchymal tumours, several malignant tumours of epithelial origin also exhibit a reactivation of HMGA2. Herein, a second main focus was laid on tumours of the thyroid gland. Although many of them can accurately be classified presurgically by fine-needle aspiration biopsies, some entities represent a diagnostic challenge. Because the cell morphology of adenomas and follicular carcinomas is identical, it is virtually impossible to discriminate follicular neoplasias by cytology alone. It was shown that HMGA2 is strongly expressed in thyroid carcinomas of follicular origin by qRT-PCR as well as by immunohistochemistry, suggesting that HMGA2 has the potential to serve as a marker in the diagnosis of thyroid tumours. |
Keywords: | Uterine leiomyomas; thyroid carcinomas; follicular neoplasia; HMGA2; PLAG1 | Issue Date: | 28-Jan-2014 | Type: | Dissertation | Secondary publication: | no | URN: | urn:nbn:de:gbv:46-00103635-15 | Institution: | Universität Bremen | Faculty: | Fachbereich 02: Biologie/Chemie (FB 02) |
Appears in Collections: | Dissertationen |
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