International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 92 - THE MOLECULAR DIFFERENCE BETWEEN RHABDOMYOSARCOMA CAUSED BY PATCHED- AND P53- MUTATIONS

Hahn H
University of Göttingen, Federal Republic of Germany

Co-Authors: 1) Kappler R, 1) Bauer R, 2) Calzada-Wack J, 2) Rosemann M, 1) Hemmerlein B
Institutions: 1) University of Göttingen, Federal Republic of Germany 2) GSF-National Research Center for Environment and Health, Neuherberg, Federal Republic of Germany

Rhabdomyosarcomas (RMS) are a heterogeneous group of tumors with respect to their molecular basis, degree of differentiation, histology, and clinical behavior. Because of the wide variation of tumor morphology it is often difficult to distinguish between subtypes of RMS. It is expected that a better understanding of the molecular changes in these tumors will help to establish a better classification system leading to an improved treatment of the disease. Up to date no report is available regarding the correlation between the genetic etiology of human RMS and their molecular profiles. This is because the genetic factors of human RMS are complex and very difficult to determine. Therefore, we compared the molecular profiles of two murine RMS models with defined primary genetic defects. Here we report that in comparison to p53-dependent RMS, RMS of heterozygous Patched1 (Ptch1) mice show a less aggressive growth and are histologically more differentiated. By means of cDNA microarray analysis, we demonstrate that tumors of Ptch1 mutants predominantly express various myogenic markers like myosin, myoglobin, and troponin , whereas tumors in p53 mutants display higher expression levels of cell cycle-associated genes like cyclin B1, cyclin-dependent kinase 2, cyclin-dependent kinase 2-associated protein 1, and cell division cycle 2. Ptch1-associated RMS are also clearly distinct from those that are p53-dependent when hierarchical clustering is performed on the data set. These results demonstrate that different causative mutations lead to distinct molecular characteristics in RMS. These differences may allow for the identification of new, gene mutation- and expression-specific treatments of these tumors.


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