TY - GEN A1 - Bortz, Birgit A1 - Marczok, Stefanie A1 - Pospisil, Heike T1 - Genomweite Identifizierung von chromosomalen Bruchpunkten bei Tumoren unterschiedlicher Gewebe T2 - Wissenschaftliche Beiträge 2016 N2 - Aufgrund der jährlich ansteigenden Anzahl an Krebsneuerkrankungen und der tödlichen Verläufe von malignen Tumoren gewinnt die vollständige Aufklärung der Tumorgenese und -progression immer mehr an Bedeutung. Für diese können Untersuchungen zu Bruchpunkten, die eine Kopienzahlvariation (CNV) in Krebsgenomen bewirken, genutzt werden. Es wurde eine Pipeline entwickelt, die in der Lage ist, CNVs, Bruchpunktregionen (BPRs) und Gene genomweit mit Hilfe von SNP-Array-Daten zu detektieren. Dazu wurden 2.820 Tumorproben aus 8 Tumorentitäten untersucht und mit 432 Proben aus gesundem Gewebe verglichen. In den Tumorproben wurden vierfach mehr BPRs detektiert, wobei unter 5 % der Gene in den Normalproben betroffen sind. Wir identifizierten 31 hochspezifische BPRs. Die am häufigsten vorkommende Variation umschließt das Gen KIAA0513, welches in Verbindung mit der Apoptose steht. Anhand der hier entwickelten Pipeline können erste Einblicke in CNV- und Bruchpunkt-Muster in Tumorgenomen gewonnen werden, die zu einem verbesserten Verständnis der Tumorgenese und somit zu einer verbesserten Diagnostik und Therapie von Krebserkrankungen führen können. N2 - The number of new cancer cases and the deadly courses of malignant tumors are still rising. An entire clarification of tumorigenesis and progression is required for better diagnostics and therapies. Here, we present an analysis of genomic breakpoint patterns, which might cause copy number variations (CNVs) in cancer genomes. Thus, a pipeline was developed which uses SNP array data for the genome-wide detection of CNVs, breakpoint regions (BPRs) and genes. 2,820 tumor samples from eight tumor entities were analyzed and compared with 432 samples from healthy tissue. Four times more BPRs were detected in the tumor samples and only less than 5 % of the affected genes were found to be involved in healthy tissues. We identified 31 highly specific BPRs. The most commonly occurring variation found in our study encloses the KIAA0513 gene, which is associated with apoptosis. Based on these results, new insights in tumorigenesis are expected. Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-5286 SN - 0949-8214 VL - 20 SP - 7 EP - 14 ER - TY - JOUR A1 - Marczok, Stefanie A1 - Bortz, Birgit A1 - Wang, Chong A1 - Pospisil, Heike T1 - Comprehensive Analysis of Genome Rearrangements in Eight Human Malignant Tumor Tissues JF - PLoS ONE N2 - Carcinogenesis is a complex multifactorial, multistage process, but the precise mechanisms are not well understood. In this study, we performed a genome-wide analysis of the copy number variation (CNV), breakpoint region (BPR) and fragile sites in 2,737 tumor samples from eight tumor entities and in 432 normal samples. CNV detection and BPR identification revealed that BPRs tended to accumulate in specific genomic regions in tumor samples whereas being dispersed genome-wide in the normal samples. Hotspots were observed, at which segments with similar alteration in copy number were overlapped along with BPRs adjacently clustered. Evaluation of BPR occurrence frequency showed that at least one was detected in about and more than 15% of samples for each tumor entity while BPRs were maximal in 12% of the normal samples. 127 of 2,716 tumor-relevant BPRs (termed ‘common BPRs’) exhibited also a noticeable occurrence frequency in the normal samples. Colocalization assessment identified 20,077 CNV-affecting genes and 169 of these being known tumor-related genes. The most noteworthy genes are KIAA0513 important for immunologic, synaptic and apoptotic signal pathways, intergenic non-coding RNA RP11-115C21.2 possibly acting as oncogene or tumor suppressor by changing the structure of chromatin, and ADAM32 likely importance in cancer cell proliferation and progression by ectodomain-shedding of diverse growth factors, and the well-known tumor suppressor gene p53. The BPR distributions indicate that CNV mutations are likely non-random in tumor genomes. The marked recurrence of BPRs at specific regions supports common progression mechanisms in tumors. The presence of hotspots together with common BPRs, despite its small group size, imply a relation between fragile sites and cancer-gene alteration. Our data further suggest that both protein-coding and non-coding genes possessing a range of biological functions might play a causative or functional role in tumor biology. This research enhances our understanding of the mechanisms for tumorigenesis and progression. Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6607 SN - 1932-6203 VL - 11 IS - 7 ER -