International Cancer Genome Consortium

Prostate cancer is the most frequent malignant tumor in males and the second most frequent cause of cancer-related death. Currently, in Germany, more than 60,000 prostate cancers are diagnosed every year. Although most of these patients are treated in a curative attempt, more than 10,000 German men die from prostate cancer annually. Owing to the demographic changes of our society, a further doubling of prostate cancer incidences during the next 20 years is expected.

Prostate cancer is generally considered a tumor of elderly men. However, a fraction of prostate cancers are diagnosed at the age of 50 years or less. For several reasons, these “early onset prostate cancers” may represent a key entity for the understanding of prostate cancer biology: First, it is likely that early onset prostate cancers represent a distinct molecular subgroup of PCA, potentially characterized by relatively small numbers of genetic changes, some of which may be particularly strong driver mutations for PCA development. Second, a fraction of prostate cancers in young individuals could represent classical prostate cancers that are detected at a very early stage and might therefore have accumulated molecular changes/mutations occurring that are most instrumental for prostate cancer early detection. Third, PCA with hereditary backgrounds are likely to accumulate in the age group below 50 years. A comparison with other sample sets (e.g. from other ICGC consortia), a systematic genomic analysis of young men with PCA could therefore lead to the detection of mechanisms for hereditary PCA. Fourth, a better understanding of these tumors is particularly relevant as finding optimal treatment regimens is most critical in young cancer patients.

We will analyze the entire genomic DNA sequences of at least 250 PCA (and matched non-tumorous DNA) of young men (≤ 50y), to at least 30 fold coverage. Genomic structural variations will be detected using large-paired-end sequencing of the same samples. In addition, we will conduct complementary molecular analyses on methylation, mRNA, and miRNA levels. The collection of tissues will take place at the University Medical Center Hamburg-Eppendorf. Sequencing will be performed at DKFZ and NCT (Heidelberg), EMBL (Heidelberg), and MPIMG (Berlin). Data management and bioinformatic data analyses will be conducted at DKFZ.

• Holger Sültmann, German Cancer Research Center, Heidelberg
• Guido Sauter, University Medical Center, Hamburg