Welcome to the eilslabs

The eilslabs form a joint research group between the division "Theoretical Bioinformatics" at the German Cancer Research Center (dkfz) and the department Bioinformatics and Functional Genomics at the Institute of Pharmacy and Molecular Biotechnology (IPMB) at Heidelberg University. The group is headed by Prof. Roland Eils.

 


x chromsome hypermutationThe eilslabs have published a new study based on a cross-cancer comparison of mutational patterns across 402 whole genomes, comprising a diverse set of childhood and adult tumors including both solid and hematopoietic malignancies. In the study, which involved the eilslabs Computational Oncology and Theoretical Systems Biology group and which was led by Natalie Jäger and Roland Eils, we 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. Whole genome sequencing of clonally expanded hematopoietic stem/progenitor cells (HSPCs) from healthy females revealed no X chromosome hypermutation. Our 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 tumourigenesis. This finding has important implications for our understanding of how tumor cells, and in particular the DNA repair machinery, respond to early oncogenic stresses. Insights into mutational patterns like X hypermutation may further bring a deeper understanding of tumor evolution and the fundamental mutagenic processes behind cancer, and allow the identification of new risk factors and/or ways of stopping these mutational processes.

Figure: Schematic view of X Chromosome Hypermutation. In tumor cells, the inactive X-chromosome (left) acquires far more mutations (orange symbols) than the active X-chromosome (right) ©: Kai Ludwig, LANGEundPFLANZ, Speyer, Germany

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