This subproject will enable a comprehensive understanding of the genomes, transcriptomes and epigenomes of fusion-driven sarcomas in temporal and spatial resolution - including the single cell level. To this end, we will extend the established workflows of the precision oncology programs INFORM and NCT/DKFZ/DKTK MASTER beyond the current standard and include patients in this process. Molecular characterization will include whole genome and RNA sequencing of entire sarcoma cell populations as well as DNA and combined RNA/ATAC sequencing at the single cell level.

Key objectives:

1. Extend the proven clinical workflows of the INFORM and NCT/DKFZ/DKTK MASTER precision oncology programs beyond the current standard of care, involving sarcoma patients and their organizations

2. Generate a comprehensive understanding of the genomes, transcriptomes and epigenomes of fusion-driven sarcomas at different time points of disease progression through systematic mapping at single cell and spatial resolution

3. Bioinformatic inference of phylogenetic relationships between individual sarcoma cells to identify intratumoral heterogeneity, selective clonal sweeps and molecular drivers of clonal evolution and therapy resistance and to nominate potential biomarkers by integration with transcriptomic and proteomic data generated in SP 2 and 4 and clinical information collected in SP 6.

PI: Stefan Fröhling, DKFZ and NCT Heidelberg, Im Neuenheimer Feld 280, Heidelberg
Co-PI: Supat Thongjuea, DKFZ and KiTZ, Im Neuenheimer Feld 280, Heidelberg