Since 2010 our group has been a leading group in the development of bioinformatic approaches for whole cancer genome approaches.
- Together with Peter Lichter, Roland Eils has initiated the ICGC PedBrain Tumor project as the first German contribution to the International Cancer Genome Consortium (ICGC) on pediatric brain tumors funded since 2010 jointly by the German Cancer Aid and the BMBF. Later, the group of Roland Eils also acquired responsibility for the data analysis and management in two further BMBF-funded ICGC projects on early-onset prostate cancer and malignant lymphoma as well as in DEEP, the German contribution to the International Human Epigenome Consortium (IHEC).
- In the first large-scale whole genome sequencing of 125 cases of medulloblastoma, the most common malignant brain tumor in children, the Eils group together with the PedBrain partners identified important biological events such as tetraploidy and recurrent mutations, which often occur in subgroup-specific patterns. This enhances our understanding of the genomic complexity and heterogeneity underlying medulloblastoma (Jones et al., 2012 Nature).
In a second ICGC PedBrain Tumor study on pilocytic astrocytoma (PA), the group performed data analysis on 96 tumor whole-genomes. They identified alterations affecting the MAPK signaling pathway in all tumors, with no other significant mutations occurring outside of this pathway. PA is therefore a prototypic single-pathway disease, and a useful model for studying the effects of MAPK signaling disruption in cancer (Jones et al., 2013 Nat Genet).
- In one of the first cross-cancer comparison study of mutational patterns across 402 whole genomes, the Eils group found that the inactive X chromosome of many cancer genomes of female patients accumulates up to four times as many somatic mutations per megabase when compared to the individual autosomes. Since the effect does not occur in healthy cells, these data suggest that hypermutation of the inactive X chromosome results from DNA replication stress in aberrantly proliferating cells, and is an early and frequent feature of tumorigenesis (Jäger et al., 2013 Cell).
- Together with partners at the European Pancreas Center / Heidelberg University Hospital (Prof. Büchler/Werner), HI-STEM gGmbH (Prof. Trumpp) and NCT (Prof. Jäger, Dr. Springfeld) we have initiated an ambitious program on the stratification of pancreatic tumors. The program combines the generation of individualized orthotopic mouse xenografts and individualized tumor-initiating cell lines with whole genome sequencing and accompanying molecular profiling of samples followed by integrative data analysis and the development of systems biology models. This aims to provide a detailed understanding of tumor initiation and progression in this highly malignant disease. The sequencing studies have initially been funded by DKFZ-HIPO and under the coordination of Roland Eils the proposal was selected for funding through the BMBF’s new systems medicine program e:MED in 2013.