Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic "androgen-type" pathomechanism in EO-PCA.

Human serum and other body fluids are rich resources for the identification of novel biomarkers, which can be measured in routine clinical diagnosis. microRNAs are small non-coding RNA molecules, which have an important function in regulating RNA stability and gene expression. The deregulation of microRNAs has been linked to cancer development and tumor progression. Recently, it has been reported that serum and other body fluids contain sufficiently stable microRNA signatures. Thus, the profiles of circulating microRNAs have been explored in a variety of studies aiming at the identification of novel non-invasive biomarkers.In this review, we discuss recent findings indicating that circulating microRNAs are useful as non-invasive biomarkers for different tumor types. Additionally, we summarize the knowledge about the mechanism of microRNA release and the putative functional roles of circulating microRNAs. Although several challenges remain to be addressed, circulating microRNAs have the potential to be useful for the diagnosis and prognosis of cancer diseases.

Our understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. Herein, transcriptome-wide expression profiles of a unique cohort of 20 laser-resected pulmonary metastases (Mets) of 18 patients with clear-cell renal cell carcinoma (RCC) were analyzed to identify expression patterns associated with two important prognostic factors in RCC: the disease-free interval (DFI) after nephrectomy and the number of Mets per patient. Differentially expressed genes were identified by comparing early (DFI 9 months) and late (DFI 5 years) Mets, and Mets derived from patients with few ( 8) and multiple ( 16) Mets. Early and late Mets could be separated by the expression of genes involved in metastasis-associated processes, such as angiogenesis, cell migration and adhesion (e.g., PECAM1, KDR). Samples from patients with multiple Mets showed an elevated expression of genes associated with cell division and cell cycle (e.g., PBK, BIRC5, PTTG1) which indicates that a high number of Mets might result from an increased growth potential. Minimal sets of genes for the prediction of the DFI and the number of Mets per patient were identified. Microarray results were confirmed by quantitative PCR by including nine further pulmonary Mets of RCC. In summary, we showed that subgroups of Mets are distinguishable based on their expression profiles, which reflect the DFI and the number of Mets of a patient. To what extent the identified molecular factors contribute to the development of these characteristics of metastatic spread needs to be analyzed in further studies. ' UICC Key words: kidney cancer; lung metastases; oligonucleotide microarraysIn numerous tumour types, the development of metastases (Mets) causes the patients' death. The median survival of renal cell carcinoma (RCC) patients amounts to merely 6 to 12 months after Mets have been diagnosed. 1 RCC is the urological cancer with the highest percentage of tumour-related deaths 2 because metastasis occurs in about 60% of the patients. 3 The preferential localization of RCC Mets is the lung. 1 In contrast to the emerging development of molecular-based therapies for RCC in the last few years, 3 molecular prognostic markers are still missing. Despite the knowledge of several molecular factors involved in metastatic spread like angiogenesis, cell adhesion, invasion or migration, 4,5 little is known about specific characteristics of this complex process. These are, for example, primary-dependent site-specific metastasis, 6 varying dormancy periods of Mets originating from the same primary tumour entity causing disease-free intervals (DFI) ranging from several months to many years, or the differing number of Mets in patients with the same primary tumour. Knowing the molecular fundamentals of these phenomena would support the prognosis of patients' outcome and facilitate the decision for an appropriate therapy regime, particularly in RCC where the DFI and the number of Mets are important predictors of clinical...