Sarcomas are rare malignant tumors of mesenchymal origin and primarily occur in children, adolescents and young adults. With multimodal treatment concepts survival has significantly improved and is now in the range of 60–70 %. Following relapse or metastasis, however, the prognosis still is poor as is also the case for patients presenting with primary disseminated disease. TranSaR-Net aims to develop novel treatment strategies overcoming tumor cell resistance directed against novel targets. To achieve this goal the German pediatric, adolescent and adult sarcoma research groups have formed a collaborative network linking the nationwide and European trial groups with access to over 90 % of all pediatric and adolescent sarcoma patients and a large number of adult sarcoma patients to basic and translational sarcoma research groups. Within TranSaRNet a registry for patients at relapse is established as target cohort for innovative treatment strategies as well as a biomaterial banking network in order to facilitate the availability of tumor and other biomaterial for basic and translational research. A joint bioinformatics platform will integrate existing array data, to standardize laboratory and evaluation procedures and for modeling new theoretical concepts in a joint effort. Within the basic and translational research work packages, the sarcoma research groups in Germany have coordinated their research activities in a joint effort. The basic research work package (WP1) includes projects on genomic (WP1.1) and epigenetic (WP1.2) tumor characterization as well as identification of the tumor initiating cell (WP1.3) and resistance mechanisms (WP1.3 und 1.4), and the identification of new targets in apoptotic pathways (WP1.4, 2.4) and tumor-induced angiogenesis (WP1.5). The translational research work package (WP2) is focused on innovative immunological treatment strategies including sarcoma specific T-cells (WP2.1), dendritic cells (WP2.2), NK- cells (WP2.4) and tumor imaging (WP2.3). A brief overview of the projects will be provided.
Despite significant improvements of survival in patients with localized osteosarcoma, about 30–40% of the patients still die on tumor progression or relapse. In order to improve therapeutic outcome we postulate the need for individualized intervention schemes based on biological characteristics of the tumor. Identification of molecular changes important for pathogenesis and tumor progression is complicated by the complex karyotype of the tumor with numerous structural and numerical alterations. Here we describe the use of Affymetrix single nucleotide polymorphism arrays in a genome wide high-resolution approach to assay both loss of heterozygosity and variations in DNA copy numbers in 46 osteosarcoma biopsy samples. We combined established histological response parameters with our genetic findings to predict prognosis. We found that overall chromosomal changes in osteosarcoma are good predictors of response to chemotherapy and outcome. Analyzing the minimal recurrent regions harbouring chromosomal alterations we expanded our investigations towards identification of gains and losses of chromosomal material and found candidate genes as potential prognostic parameters and therapeutic targets. Identified genomic regions and genes were validated by mRNA-expression studies and correlated with proteom analysis by MALDI Imaging. Thus, structural chromosomal alterations detected by SNP analysis may serve as a simple but robust parameter to predict response to chemotherapy. The results also indicate that we are able to identify several genomic loci with high potential to predict the outcome of the disease. Furthermore new potential target genes were identified by this genome wide screen. The project is part of the Translational Sarcoma Research Network (TransSaRNet).
