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Selected Publication:
Flicker, K.
Characterization of genomic changes in different tumor types by array-CGH
[ Dissertation ] Medical University of Graz; 2013. pp. 139
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- Authors Med Uni Graz:
- Flicker Karin
- Advisor:
- Geigl Jochen Bernd
- Petek Erwin
- Speicher Michael
- Altmetrics:
- Abstract:
- Copy number alterations are frequently seen in tumor genomes and they are considered as potentially important in tumor evolution. Copy number alterations also may act as a driving force for tumorigenesis and for tumor progression, moreover, an altered gene expression may determine the fate of a cell or the phenotype of an organism. This thesis provides information regarding copy number changes in three different tumor entities. Part I of this dissertation describes the characterization of the MTC genome by array-CGH (comparative genomic hybridization) and M-FISH (multiplex fluorescent in situ hybridization). Hereditary and sporadic medullary thyroid carcinoma (MTC) are closely associated with RET proto-oncogene mutations. However, the role of additional changes in the tumor genomes remains unclear. The objective of the project was the identification of chromosomal regions involved in MTC tumorigenesis and to assess their significance by using MTC derived cell lines. Array-CGH was employed to map chromosomal imbalances in 52 primary tumors and 10 metastases. Furthermore, 5 MTC cell lines were characterized by M-FISH in detail and the tumorigenicity of three cell lines was evaluated by severe combined immunodeficiency (SCID)-mouse experiments. The MTC data suggest that - in contrast to most other tumor entities ¿ this tumor entity does not acquire a multitude of genomic imbalances. Part II of this dissertation describes copy number changes in uterine smooth muscle tumors as assessed by array-CGH. In section I array-CGH was employed to map copy number changes in 4 endometrial stromal nodules (ESN) cases, 22 endometrial stromal sarcomas (ESS) cases and 4 undifferentiated endometrial sarcomas (UES) cases. The results indicate a low number of copy number variations in ESN and a high number of gains and losses in ESS and UES. The number of aberrations directly correlates with their histological grading and clinical behavior. In section II 20 leiomyoma (LM) cases, 14 atypical leiomyoma (at-LM) and 13 leiomyosarcoma (LMS) were analyzed for their presence of gains and losses in their genome. The results show that LM harbor a low number of copy number variations followed by an increase in gains and losses in at-LM and LMS. Atypical LM and LMS share several copy number variations in their genome which may propose a similar genetic pathway involved in their evolvement.