International Cancer Genome Consortium

Brain tumors in recent years have replaced leukemia as the leading cause of cancer-related mortality in children, despite the fact that they occur only half as frequent as leukemia in this age group. Additionally, these children suffer from severe morbidity caused by neurosurgical procedures at sensitive anatomical sites performed in a vulnerable phase of brain development as well as by long term neurological, cognitive, endocrinological, cardiac, and psychological side effects of the intensive multi-modal adjuvant therapy regimens. In the PedBrain Tumor contributing study, the main focus lies on the two most frequent brain tumors in childhood, namely medulloblastoma and pilocytic astrocytoma, both of which were explicitly mentioned as especially relevant pediatric entities in the published ICGC guidelines.

On the basis of genome sequencing, we will carry out a comprehensive analysis of pediatric brain tumors. Genomic sequence analysis will be complemented by detailed transcriptome and methylome analyses. The molecular data will be related to clinical parameters for the identification of novel prognostic and predictive markers as well as therapy targets. To this aim, a unique network of outstanding expertise has been formed with an exceptional collection of tumors with well-documented molecular and clinical characteristics. Internationally renowned experts on the identification of genomic rearrangements and DNA mutations use various methods such as paired end mapping, and high throughput genome, transcriptome and methylome sequencing to gain multiple datasets for each tumor type.

An extraordinary challenge is the analysis and storage of the gigantic mass of data that are produced in the course of this study. The genome of a cell is composed of about three billion building blocks, which are captured up to 30 times in the various analyses in order to verify results. A storage capacity of several petabytes (a petabyte is equal to one million gigabytes) will be established in Heidelberg in connection with this project.

The German ICGC contribution is coordinated by Professor Peter Lichter from the German Cancer Research Center. All data of the German ICGC project will be joined together by Professor Roland Eils, the network’s deputy coordinator.
Further indispensible subproject leaders and institutions involved in the PedBrain Tumor project include: Prof. Christof von Kalle, National Center for Tumor Diseases, Heidelberg; Dr. Jan Korbel, European Molecular Biology Laboratory, Heidelberg; Dr. Stefan Pfister, Heidelberg University Hospital and DKFZ; Prof. Hans Lehrach, Max Planck Institute for Molecular Genetics, Berlin; and Prof. Guido Reifenberger Düsseldorf University Hospital.