DARWIN Digitale Dissertationen German Version Strich

FU Berlin
Digitale Dissertation

Kerstin Kaltenberg :
Mutationanalysis from tumorsuppressorgene PTEN in prostate cancers
Mutationsanalyse vom Tumorsuppressorgen PTEN (phosphatase and tensin homolog deleted on chromosome ten) in Prostatakarzinomen

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Abstract

Our work shall make a contribution to the clarification of the question whether the loss of the tumorsuppressorgene PTEN can be proved at the prostate cancer and whether a connection between the genesis of the prostate cancer and the gene in question exists. The PTEN / MMAC1 / TEP1 gene, located at 10q23.3, is a tumorsuppressorgene responsible for the familial cancer syndromes Cowden disease and Bannayann-Zonana syndrome, and is commonly somatically mutated in several types of cancers. Mutations of the PTEN gene have been found in prostate cancer cell lines and LOH (loss of heterozygosity) at 10q23.3 in prostate tumors have also been discript with a high frequency. To determine the role of this gene in prostate tumorigenesis, we therefore analysed 40 primary tumors for loss of heterozygosity (LOH) within the 10q22-23 region such that tumors hemizygous at those loci may be examined for somatic PTEN mutations. Loss of heterozygosity was found in 14 (35%) of the 40 tumors DNAs. Among these 6 tumors exhibited allele loss in the marker D10S2491 wherein lies the PTEN gene. We searched the entire coding region of PTEN for somatic mutation in these 14 tumors. 4 somatic mutations were detected. These results suggest the assumption that (mutation-caused) deactivations of the PTEN only one part aspect in the context of a more complex process represent that is responsible for the genesis of prostate cancer. The fact that mutations of PTEN could be also proved in a multitude of other tumors (the other name of PTEN = MMAC1/ mutated in multiple advanced cancers 1 indicate in the direction) allows speculations on a "Mitbeteiligung" of the PTEN however in the tumorigenesis of the prostate cancer. For an objective assessment of the role of PTEN during the genesis of primary prostate cancer is a taller number of examined patients necessary.

Table of Contents

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0. Titelblatt, Inhaltsverzeichnis
1. Einleitung 3
2. Material und Methoden 16
2.1. Material 16
2.2. Methoden 20
3. Ergebnisse 33
3.1. Untersuchungen zu LOH 38
3.2. Nachweis von Mutationen bei Tumorgeweben mit LOH 45
4. Diskussion 52
5. Zusammenfassung 61
Danksagung 63
Kurzbiographie 64
Literaturverzeichnis 65

More Information:

Online available: http://www.diss.fu-berlin.de/2002/154/indexe.html
Language of PhDThesis: german
Keywords: PTEN prostate cancer mutation tumorsuppressorgene
DNB-Sachgruppe: 33 Medizin
Date of disputation: 13-Sep-2002
PhDThesis from: Fachbereich Humanmedizin, Freie Universität Berlin
First Referee: Priv.-Doz. Dr. med Markus Müller
Second Referee: Prof.Dr.med. Martin Digweed
Contact (Author): k.g.Kaltenberg@t-online.de
Contact (Advisor): markus.mueller@medizin.fu-berlin.de
Date created:15-Aug-2002
Date available:22-Aug-2002

 


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