Genetische Aberrationen mit einem Wachstumsvorteil in frühen Präkanzerosen des Urothels der Harnblase

Bladder cancer is the second common malignant urological neoplasia. Most of the tumors are superficial (80%) at first diagnosis and reccur frequently. In order to understand the initial genetic aberrations reflecting growth advantage in bladder cancer we investigated first chromosomal aberrations and validated their biological potential at single cell level. Using multi-colour fluorescence in situ hybridisation (FISH; Urovysion) and Ki-67 immunohistochemistry first data was aquired and completed by laser-microdissecting single cells for single-cell comparative genomic hybridisation (CGH) analy-ses. Double staining of fluorescence in situ hybridisation (Urovysion, Vysis/Abbott) and Ki-67 immunohistochemistry was carried out on frozen tissue sections from 25/40 patients with pre-cancerous lesions of the bladder (13 hyperplasia, 12 dysplasia; those with preferably primary diagnosis; and further specimen from 7 carcinoma in situ, 3 pTaG1, 4 pT1G3). In addition 55 single cells of these precancerous lesions were laser-microdissected and analysed with single cell comparative genomic hybridisation (CGH). Focussing on the proliferating cells versus their non-proliferative neighbourhood in precan-cerous lesions of the bladder, chromosomal aberrations were detected in both types of cells. Proliferating hyperplastic cells showed almost a normal, diploid FISH and no further loss of chromosomal loci in the CGH-analysis. The CGH data of dysplasia cells showed mainly a loss of the chromosomal region 9p21 in proliferating cells, like expected from FISH results. Other chromosomal aberrations, depicted in dysplasia cells, were deletion of chromosome 9 and 13q as well as amplifications of the chromosomes 9p, 12p, 17q, 18p, 22, X and Y. In this regions many candidate genes, involved in regulation of cell proliferation and differentiation, apoptosis and metabolism, are located. These methods established are apt to show that genetic aberrations detected in early bladder lesions or normal urothelium are biologically relevant since found in proliferating cells. This work has been supported by the German Science Foundation (DFG, grant no: Kn263/9-2).

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2008

Author dc:creator

• Koufou, Stella Vasiliki

Contributors dc:contributor

• Knüchel-Clarke, Ruth

• info:eu-repo/classification/ddc/570
• Präkanzerose
• Blasentumor
• Fluoreszenz-in-situ-Hybridisierung
• Immuncytochemie
• Mikrodissektion
• Tumorwachstum
• Frühcarcinom
• Krebszelle
• Carcinogenese
• Krebsforschung
• Biowissenschaften, Biologie
• Genetische Aberration
• Komparative Genomische Hybridisierung
• Einzelzell-/Gesamt-genomische Amplifikation
• Linker-adaptor PCR
• In-situ-hybridisation
• Whole genomic amplification
• Single Cell
• Carcinogenesis
• bladdercancer

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-112669%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50112