Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Molecular-cytogenetic and gene expression study of adenocarcinomas and its possible precursor lesions

Abstract
Adenocarcinomas (AC) have become the major group of lung carcinomas in Austria as well as world-wide. In the last decade precursor lesions of AC especially atypical adenomatous hyperplasia have gained particular interest.
One intention of the submitted project is the identification of oncogenes and tumorsuppressor genes responsible for progression and differentiation of ACs. The expression of these genes will also be checked at the protein level. As a result of this study we hope to find several biomarkers easily detectable by usual immunhistochemistry and therefore feasible for clinical routine. However, we additionally want to enlight another aspect. Tumor cells are following the evolutionary priniciple, making the most fittest clone the pivotal one. Under this view we will investigate, how tumor cells react to gross chromosomal aberrations. In our opinion, first the cells have to reestablish a kind of balance in order to stay alive, and second, they have to adapt their biochemical pathways in order to fully exploit the growth advantage provided by the genetic alteration. For example, there would be no use of a high copy amplified oncogene, if it has to form a heterodimer with an other not overrepresented protein in order to exert its influence. By this analysis we hope to get further insights into transcriptional control and to elucidate interconnected genes and redundant pathways. Taking advantage of the tremendous progress of the Human Genome Project we also want to reveal sequence dependency of selected chromosomal breakpoints. Integration of sequence data and gene expression data for genes in the vicinity of the breakpoints should clarify the question why some chromosomal sites are more vulnerable than others and why this preference is tissue and tumor specific in many cases. This study will utilize Comparative Genomic Hybridization (CGH), microarray CGH and gene expression studies as well as immunhistochemistry and FISH on tissuearrays.
Lokale Teilprojektleitung:
Popper Helmuth
Laufzeit:
01.01.2000-30.09.2006
Programm:
EU COST
Art der Forschung
Angewandte Forschung
Mitarbeiter*innen
Popper, Helmuth, Projektleiter*in
Beteiligte MUG-Organisationseinheiten
Diagnostik und Forschungsinstitut für Pathologie
Projektpartner
Medizinische Universität Wien (MUW), Österreich
St. Anna Kinderspital, Österreich
Gefördert durch
Europäische Kommission, Rue de la Loi, Brussels, Belgien
Publizierte Projektergebnisse
> Immunohistochemistry-Based Tissue Microarray Analy... Arch Pathol Lab Med. 130: 1393-1394.-The College of American Pathologists 2006 Annual Meeting (CAP `06); SEP 10-13, 2006; San Diego, USA.
> Differences in growth signaling pathway activation... European Respiratory Society Annual Congress 2006; SEP 2-6, 2006; Munich, GERMANY. 2006.
> Complex chromosomal aberrations in pulmonary adeno... MODERN PATHOL 2005 18: 316A-317A.
> Complex chromosomal aberrations in pulmonary adeno... LAB INVEST 2005 85: 316A-317A.
> Protein expression profiles in adenocarcinomas and... J PATHOL. 2004; 203(3): 798-807.
> Bronchiolar columnar cell dysplasia--genetic analy... Virchows Arch. 2003; 442(5):429-436
> Is high-grade adenomatous hyperplasia an early bro... J Pathol. 2003; 201(3):371-376
> Bronchiolar columnar cell dysplasia - Genetic anal... LAB INVEST 2002 82: 1373-1373.
> Comparative genomic hybridization and cytogenetic ... Int J Oncol. 2001; 18(5):923-928
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