Multi-omics approach including structural variations in the genome of medulloblastoma to detect novel targets

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Pediatric brain tumors are the leading cause of cancer-related death in children. Despite considerable advances in basic research and clinical treatment of these tumors, there is still an urgent need for more effective therapies, especially for malignant brain tumors such as medulloblastoma. Compared to transcriptional, genetic and epigenetic profiles, the genomic landscape of medulloblastomas with regard to structural DNA variations (SVs) is so far less well characterized. A comprehensive identification of SVs in medulloblastomas and the characterization of molecular pathomechanisms that drive tumor growth as a result of these SVs are therefore urgently required, not the least for the development of new, more effective treatment approaches. Therefore, we will carry out a highly integrative “multi-omics” approach including long-read sequencing of medulloblastomas in this project in order to comprehensively characterize the SVs in these tumors and to discover novel oncogenic drivers. We will perform a de novo genome assembly on our molecularly (including DNA methylation, copy number analysis, RNA sequencing, and phospho-proteome profiling) and clinically well characterized cohort of 40 medulloblastoma patients. These newly generated data will be analyzed in a multidimensional approach and will thus provide a comprehensive overview of the genomic landscapes including the SVs in these tumors, which in turn will significantly improve the understanding of medulloblastoma pathogenesis and thereby reveal evidence for novel therapeutic targets.