TY - JOUR A1 - Ludwig, Nicole A1 - Werner, Tamara V. A1 - Backes, Christina A1 - Trampert, Patrick A1 - Gessler, Manfred A1 - Keller, Andreas A1 - Lenhof, Hans-Peter A1 - Graf, Norbert A1 - Meese, Eckart T1 - Combining miRNA and mRNA Expression Profiles in Wilms Tumor Subtypes JF - International Journal of Mokecular Sciences N2 - Wilms tumor (WT) is the most common childhood renal cancer. Recent findings of mutations in microRNA (miRNA) processing proteins suggest a pivotal role of miRNAs in WT genesis. We performed miRNA expression profiling of 36 WTs of different subtypes and four normal kidney tissues using microarrays. Additionally, we determined the gene expression profile of 28 of these tumors to identify potentially correlated target genes and affected pathways. We identified 85 miRNAs and 2107 messenger RNAs (mRNA) differentially expressed in blastemal WT, and 266 miRNAs and 1267 mRNAs differentially expressed in regressive subtype. The hierarchical clustering of the samples, using either the miRNA or mRNA profile, showed the clear separation of WT from normal kidney samples, but the miRNA pattern yielded better separation of WT subtypes. A correlation analysis of the deregulated miRNA and mRNAs identified 13,026 miRNA/mRNA pairs with inversely correlated expression, of which 2844 are potential interactions of miRNA and their predicted mRNA targets. We found significant upregulation of miRNAs-183, -301a/b and -335 for the blastemal subtype, and miRNAs-181b, -223 and -630 for the regressive subtype. We found marked deregulation of miRNAs regulating epithelial to mesenchymal transition, especially in the blastemal subtype, and miRNAs influencing chemosensitivity, especially in regressive subtypes. Further research is needed to assess the influence of preoperative chemotherapy and tumor infiltrating lymphocytes on the miRNA and mRNA patterns in WT KW - miRNA KW - Wilms tumor KW - blastemal KW - regressive Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165430 VL - 17 IS - 4 ER - TY - JOUR A1 - Schmitt, Jana A1 - Backes, Christina A1 - Nourkami-Tutdibi, Nasenien A1 - Leidinger, Petra A1 - Deutscher, Stephanie A1 - Beier, Markus A1 - Gessler, Manfred A1 - Graf, Norbert A1 - Lenhof, Hans-Peter A1 - Keller, Andreas A1 - Meese, Eckart T1 - Treatment-independent miRNA signature in blood of wilms tumor patients JF - BMC Genomics N2 - Background Blood-born miRNA signatures have recently been reported for various tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients prior and after preoperative chemotherapy according to SIOP protocol 2001. Results We did not find a significant difference between miRNA signature of both groups. However both, Wilms tumor patients prior and after chemotherapy showed a miRNA signature different from healthy controls. The signature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients after chemotherapy an accuracy of 97.0%, each as compared to healthy controls. Conclusion Our results provide evidence for a blood-born Wilms tumor miRNA signature largely independent of four weeks preoperative chemotherapy treatment. KW - miRNA Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124034 VL - 13 IS - 379 ER - TY - JOUR A1 - Osorio, Ana A1 - Milne, Roger L. A1 - Kuchenbaecker, Karoline A1 - Vaclová, Tereza A1 - Pita, Guillermo A1 - Alonso, Rosario A1 - Peterlongo, Paolo A1 - Blanco, Ignacio A1 - de la Hoya, Miguel A1 - Duran, Mercedes A1 - Diez, Orland A1 - Ramón y Cajal, Teresa A1 - Konstantopoulou, Irene A1 - Martínez-Bouzas, Christina A1 - Conejero, Raquel Andrés A1 - Soucy, Penny A1 - McGuffog, Lesley A1 - Barrowdale, Daniel A1 - Lee, Andrew A1 - Arver, Brita A1 - Rantala, Johanna A1 - Loman, Niklas A1 - Ehrencrona, Hans A1 - Olopade, Olufunmilayo I. A1 - Beattie, Mary S. A1 - Domchek, Susan M. A1 - Nathanson, Katherine A1 - Rebbeck, Timothy R. A1 - Arun, Banu K. A1 - Karlan, Beth Y. A1 - Walsh, Christine A1 - Lester, Jenny A1 - John, Esther M. A1 - Whittemore, Alice S. A1 - Daly, Mary B. A1 - Southey, Melissa A1 - Hopper, John A1 - Terry, Mary B. A1 - Buys, Saundra S. A1 - Janavicius, Ramunas A1 - Dorfling, Cecilia M. A1 - van Rensburg, Elizabeth J. A1 - Steele, Linda A1 - Neuhausen, Susan L. A1 - Ding, Yuan Chun A1 - Hansen, Thomas V. O. A1 - Jønson, Lars A1 - Ejlertsen, Bent A1 - Gerdes, Anne-Marie A1 - Infante, Mar A1 - Herráez, Belén A1 - Moreno, Leticia Thais A1 - Weitzel, Jeffrey N. A1 - Herzog, Josef A1 - Weeman, Kisa A1 - Manoukian, Siranoush A1 - Peissel, Bernard A1 - Zaffaroni, Daniela A1 - Scuvera, Guilietta A1 - Bonanni, Bernardo A1 - Mariette, Frederique A1 - Volorio, Sara A1 - Viel, Alessandra A1 - Varesco, Liliana A1 - Papi, Laura A1 - Ottini, Laura A1 - Tibiletti, Maria Grazia A1 - Radice, Paolo A1 - Yannoukakos, Drakoulis A1 - Garber, Judy A1 - Ellis, Steve A1 - Frost, Debra A1 - Platte, Radka A1 - Fineberg, Elena A1 - Evans, Gareth A1 - Lalloo, Fiona A1 - Izatt, Louise A1 - Eeles, Ros A1 - Adlard, Julian A1 - Davidson, Rosemarie A1 - Cole, Trevor A1 - Eccles, Diana A1 - Cook, Jackie A1 - Hodgson, Shirley A1 - Brewer, Carole A1 - Tischkowitz, Marc A1 - Douglas, Fiona A1 - Porteous, Mary A1 - Side, Lucy A1 - Walker, Lisa A1 - Morrison, Patrick A1 - Donaldson, Alan A1 - Kennedy, John A1 - Foo, Claire A1 - Godwin, Andrew K. A1 - Schmutzler, Rita Katharina A1 - Wappenschmidt, Barbara A1 - Rhiem, Kerstin A1 - Engel, Christoph A1 - Meindl, Alftons A1 - Ditsch, Nina A1 - Arnold, Norbert A1 - Plendl, Hans Jörg A1 - Niederacher, Dieter A1 - Sutter, Christian A1 - Wang-Gohrke, Shan A1 - Steinemann, Doris A1 - Preisler-Adams, Sabine A1 - Kast, Karin A1 - Varon-Mateeva, Raymonda A1 - Gehrig, Andrea A1 - Stoppa-Lyonnet, Dominique A1 - Sinilnikova, Olga M. A1 - Mazoyer, Sylvie A1 - Damiola, Francesca A1 - Poppe, Bruce A1 - Claes, Kathleen A1 - Piedmonte, Marion A1 - Tucker, Kathy A1 - Backes, Floor A1 - Rodríguez, Gustavo A1 - Brewster, Wendy A1 - Wakeley, Katie A1 - Rutherford, Thomas A1 - Caldés, Trinidad A1 - Nevanlinna, Heli A1 - Aittomäki, Kristiina A1 - Rookus, Matti A. A1 - van Os, Theo A. M. A1 - van der Kolk, Lizet A1 - de Lange, J. L. A1 - Meijers-Heijboer, Hanne E. J. A1 - van der Hout, A. H. A1 - van Asperen, Christi J. A1 - Goméz Garcia, Encarna B. A1 - Encarna, B. A1 - Hoogerbrugge, Nicoline A1 - Collée, J. Margriet A1 - van Deurzen, Carolien H. M. A1 - van der Luijt, Rob B. A1 - Devilee, Peter A1 - Olah, Edith A1 - Lázaro, Conxi A1 - Teulé, Alex A1 - Menéndez, Mireia A1 - Jakubowska, Anna A1 - Cybulski, Cezary A1 - Gronwald, Jecek A1 - Lubinski, Jan A1 - Durda, Katarzyna A1 - Jaworska-Bieniek, Katarzyna A1 - Johannsson, Oskar Th. A1 - Maugard, Christine A1 - Montagna, Marco A1 - Tognazzo, Silvia A1 - Teixeira, Manuel R. A1 - Healey, Sue A1 - Olswold, Curtis A1 - Guidugli, Lucia A1 - Lindor, Noralane A1 - Slager, Susan A1 - Szabo, Csilla I. A1 - Vijai, Joseph A1 - Robson, Mark A1 - Kauff, Noah A1 - Zhang, Liying A1 - Rau-Murthy, Rohini A1 - Fink-Retter, Anneliese A1 - Singer, Christine F. A1 - Rappaport, Christine A1 - Kaulich, Daphne Geschwantler A1 - Pfeiler, Georg A1 - Tea, Muy-Kheng A1 - Berger, Andreas A1 - Phelan, Catherine M. A1 - Greene, Mark H. A1 - Mai, Phuong L. A1 - Lejbkowicz, Flavio A1 - Andrulis, Irene A1 - Mulligan, Anna Marie A1 - Glendon, Gord A1 - Toland, Amanda Ewart A1 - Bojesen, Anders A1 - Pedersen, Inge Sokilde A1 - Sunde, Lone A1 - Thomassen, Mads A1 - Kruse, Torben A. A1 - Jensen, Uffe Birk A1 - Friedman, Eitan A1 - Laitman, Yeal A1 - Shimon, Shanie Paluch A1 - Simard, Jaques A1 - Easton, Douglas F. A1 - Offit, Kenneth A1 - Couch, Fergus J. A1 - Chenevix-Trench, Georgia A1 - Antoniou, Antonis C. A1 - Benitez, Javier T1 - DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers JF - PLOS Genetics N2 - Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7x10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95% CI: 1.03-1.21, p = 4.8x10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied. KW - single-nucleotide polymorphisms KW - breast cancer KW - ovarian cancer KW - genetic modifiers KW - common variants KW - NEIL2 KW - OGG1 KW - investigators KW - consortium KW - damage Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116820 SN - 1553-7404 VL - 4 IS - e1004256 ER - TY - JOUR A1 - Keller, Andreas A1 - Leidinger, Petra A1 - Vogel, Britta A1 - Backes, Christina A1 - ElSharawy, Abdou A1 - Galata, Valentina A1 - Mueller, Sabine C. A1 - Marquart, Sabine A1 - Schrauder, Michael G. A1 - Strick, Reiner A1 - Bauer, Andrea A1 - Wischhusen, Jörg A1 - Beier, Markus A1 - Kohlhaas, Jochen A1 - Katus, Hugo A. A1 - Hoheisel, Jörg A1 - Franke, Andre A1 - Meder, Benjamin A1 - Meese, Eckart T1 - miRNAs can be generally associated with human pathologies as exemplified for miR-144* JF - BMC MEDICINE N2 - Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR. Results: We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 ( 95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait. Conclusions: Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers. KW - peripheral blood KW - microna profiles KW - disease KW - signature KW - expression KW - miRNA KW - microarray KW - biomarker KW - bioinformatics KW - lung-cancer KW - multiple sclerosis KW - gene KW - serum Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114349 SN - 1741-7015 VL - 12 ER - TY - JOUR A1 - Abu-Halima, Masood A1 - Häusler, Sebastian A1 - Backes, Christina A1 - Fehlmann, Tobias A1 - Staib, Claudia A1 - Nestel, Sigrun A1 - Nazarenko, Irina A1 - Meese, Eckart A1 - Keller, Andreas T1 - Micro-ribonucleic acids and extracellular vesicles repertoire in the spent culture media is altered in women undergoing \(In\) \(Vitro\) Fertilization JF - Scientific Reports N2 - MicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene regulation. We analyzed the potential of miRNAs secreted from pre-implantation embryos into the embryonic culture media as biomarkers to predict successful pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the SCM. On average, we detected 163 miRNAs in SCM of samples with failed pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634 predicted an embryo transfer leading to a positive pregnancy with an accuracy of 71% and a sensitivity of 85%. Among the 621 miRNAs, 102 (16.4%) showed a differential expression between positive and negative outcome of pregnancy with miR-29c-3p as the most significantly differentially expressed miRNA. The number of extracellular vehicles was lower in SCM with positive outcomes (3.8 × 10\(^9\)/mL EVs), as compared to a negative outcome (7.35 × 10\(^9\)/mL EVs) possibly explaining the reduced number of miRNAs in the SCM associated with failed pregnancies. The analysis of the miRNome in the SCM of couples undergoing fertility treatment lays the ground towards development of biomarkers to predict successful pregnancy and towards understanding the role of embryonic miRNAs found in the SCM. KW - Medicine KW - miRNAs KW - Molecular biology KW - Non-coding RNAs Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173632 VL - 7 ER -