@article{GesslerThomasCouillinetal.1989, author = {Gessler, Manfred and Thomas, G. H. and Couillin, P. and Junien, C. and McGillivray, B. C. and Hayden, M. and Jaschek, G. and Bruns, G. A.}, title = {A deletion map of the WAGR region on chromosome II}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59255}, year = {1989}, abstract = {The WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) region has been assigned to chromosome 11p13 on the basis of overlapping constitutional deletions found in affected individuals. We have utilized 31 DNA probes which map to the WAGR deletion region, together with six reference loci and 13 WAGR-related deletions, to subdivide this area into 16 intervals. Specific intervals have been correlated with phenotypic features, leading to the identification of individual subregions for the aniridia and Wilms tumor loci. Delineation, by specific probes, of multiple intervals above and below the critical region and of five intervals within the overlap area provides a framework map for molecular characterization of WAGR gene loci and of deletion boundary regions.}, subject = {Biochemie}, language = {en} } @article{GesslerBruns1989, author = {Gessler, Manfred and Bruns, G. A. P.}, title = {A physical map around the WAGR complex on the short arm of chromosome 11}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59246}, year = {1989}, abstract = {A long-range restriction map of part of the short arm of ehromosome 11 including the WAGR region has been constructed using pulsed-field gel electrophoresis and a number of infrequently cutting restriction enzymes. A total of 15.4 Mbp has been mapped in detall, extending from proximal 11p14 to the distal part of 11p12. The map localizes 35 different DNA probes and reveals at least nine areas with features eharaeteristle of BTF islands, some of which may be candidates for the different loci underlying the phenotype of the WAGR syndrome. This map will furthermore allow screening of DNA from individuals with WAGR-related phenotypes and from Wilms tumors for associated chromosomal rearrangements.}, subject = {Biochemie}, language = {en} } @article{VortkampThiasGessleretal.1991, author = {Vortkamp, A. and Thias, U. and Gessler, Manfred and Rosenkranz, W. and Kroisel, P. M. and Tommerup, N. and Kruger, G. and Gotz, J. and Pelz, L. and Grzeschik, Karl-Heinz}, title = {A somatic cell hybrid panel and DNA probes for physical mapping of human chromosome 7p}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59217}, year = {1991}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{SchwartzNeveEisenmanetal.1994, author = {Schwartz, Faina and Neve, Rachel and Eisenman, Robert and Gessler, Manfred and Bruns, Gail}, title = {A WAGR region gene between PAX-6 and FSHB expressed in fetal brain}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59125}, year = {1994}, abstract = {Developmental delay or mental retardation is a frequent component of multi-system anomaly syndromes associated with chromosomal deletions. Isolation of genes involved in the mental dysfunction in these disorders should define loci important in brain formation or function. We have identified a highly conserved locus in the distal part of 11 p 13 that is prominently expressed in fetal brain. Minimal expression is observed in a number of other fetal tissues. The gene maps distal to PAX-6 but proximal to the loci for brain-derived neurotrophic factor (BDNF) and the beta subunit of follicle stimulating hormone (FSHB), within a region previously implicated in the mental retardation component of some WAGR syndrome patients. Within fetal brain, the corresponding transcript is prominent in frontal, motor and primary visual cortex as weil as in the caudate-putamen. The characteristics of this gene, including the striking evolutionary conservation at the locus, suggest that the encoded protein may function in brain development.}, subject = {Biochemie}, language = {en} } @article{BarnekowGessler1986, author = {Barnekow, Angelika and Gessler, Manfred}, title = {Activation of the pp60\(^{c-src}\) kinase during differentiation of monomyelocytic cells in vitro}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59278}, year = {1986}, abstract = {Tbe proto-oncogene c-src, the cellular homolog of the Rous sarcoma virus (RSV) transforming gene v-src, is expressed in a tissue-specific and age-dependent manner. Its physiological function, although still unknown, appears to be more closely related to differentiation processes than to proliferation processes. To obtain more information about the physiological role of the c-src gene in cells, we have studied differentiation-dependent alterations using the human HL-60 leukaemia cell line as a model system. Induction of monocytic and granulocytic differentiation of HL-60 cells by 12-0-tetradecanoylphorbol-13-acetate (TPA) and dimethylsulfoxide (DMSO) is associated with an activation of the pp60c-src tyrosine kinase, but not with increased c-src gene expression. Control experiments exclude an interaction of TPA and DMSO themselves with the pp60c-src kinase.}, subject = {Biochemie}, language = {en} } @article{HigginsSmilinichSaitetal.1994, author = {Higgins, M. J. and Smilinich, N. J. and Sait, S. and Koenig, A. and Pongratz, J. and Gessler, Manfred and Richard III., C. W. and James, M. R. and Sanford, J. P. and Kim, B.-W. and Cattelane, J. and Nowak, N. J. and Winterpacht, A. and Zabel, B. U. and Munroe, D. J. and Bric, E. and Housman, D. E. and Jones, C. and Nakamura, Y. and Gerhard, D. S. and Shows, T. B.}, title = {An Ordered NotI Fragment Map of Human Chromosome Band 11p15}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45766}, year = {1994}, abstract = {An ordered NotI fragment map containing over 60 loci and encompassing approximately 17 Mb has been constructed for human chromosome band llpl5. Forty-two probes, including 11 NotI-linking cosmids, were subregionaUy mapped to llpl5 using a subset of the Jl-deletion hybrids. These and 23 other probes defining loci previously mapped to 11p15 were hybridized to genomic DNA digested with NotI and 5 other infrequently cleaving restriction enzymes and separated by pulsed-field gel electrophoresis. Thirty-nine distinct NotI fragments were detected encompassing approximately 85\% of the estimated length of llp15. The predicted order of the gene loci used is cenMYODI- PTH-CALCA-ST5-RBTNI-HPX-HBB-RRMlTH/ INS!1GF2-H19-CTSD-MUC2-DRD4-HRAS-RNHtel. This map wiu allow higher resolution mapping of new Ilp15 markers, facilitate positional cloning of disease genes, and provide a framework for the physical mapping of llp15 in clone contigs.}, subject = {Genom / Genkartierung / Genanalyse}, language = {en} } @article{SchmittKellerNourkamiTutdibietal.2011, author = {Schmitt, Jana and Keller, Andreas and Nourkami-Tutdibi, Nasenien and Heisel, Sabrina and Habel, Nunja and Leidinger, Petra and Ludwig, Nicole and Gessler, Manfred and Graf, Norbert and Berthold, Frank and Lenhof, Hans-Peter and Meese, Eckart}, title = {Autoantibody Signature Differentiates Wilms Tumor Patients from Neuroblastoma Patients}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0028951}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133794}, pages = {e28951}, year = {2011}, abstract = {Several studies report autoantibody signatures in cancer. The majority of these studies analyzed adult tumors and compared the seroreactivity pattern of tumor patients with the pattern in healthy controls. Here, we compared the autoimmune response in patients with neuroblastoma and patients with Wilms tumor representing two different childhood tumors. We were able to differentiate untreated neuroblastoma patients from untreated Wilms tumor patients with an accuracy of 86.8\%, a sensitivity of 87.0\% and a specificity of 86.7\%. The separation of treated neuroblastoma patients from treated Wilms tumor patients' yielded comparable results with an accuracy of 83.8\%. We furthermore identified the antigens that contribute most to the differentiation between both tumor types. The analysis of these antigens revealed that neuroblastoma was considerably more immunogenic than Wilms tumor. The reported antigens have not been found to be relevant for comparative analyses between other tumors and controls. In summary, neuroblastoma appears as a highly immunogenic tumor as demonstrated by the extended number of antigens that separate this tumor from Wilms tumor.}, language = {en} } @article{WelterWagnerFurtwaengleretal.2021, author = {Welter, Nils and Wagner, Angelo and Furtw{\"a}ngler, Rhoikos and Melchior, Patrick and Kager, Leo and Vokuhl, Christian and Schenk, Jens-Peter and Meier, Clemens Magnus and Siemer, Stefan and Gessler, Manfred and Graf, Norbert}, title = {Characteristics of nephroblastoma/nephroblastomatosis in children with a clinically reported underlying malformation or cancer predisposition syndrome}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {19}, issn = {2072-6694}, doi = {10.3390/cancers13195016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248434}, year = {2021}, abstract = {(1) Background: about 10\% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. (2) Methods: this retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. (3) Results: Genitourinary malformations (GU, N = 66, 2.3\%), Beckwith-Wiedemann spectrum (BWS, N = 32, 1.1\%), isolated hemihypertrophy (IHH, N = 29, 1.0\%), Denys-Drash syndrome (DDS, N = 24, 0.8\%) and WAGR syndrome (N = 20, 0.7\%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24.5 months vs. 39.0 months), had smaller tumors (349.4 mL vs. 487.5 mL), less often metastasis (8.2\% vs. 18\%), but more often nephroblastomatosis (12.9\% vs. 1.9\%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30\%), DDS (29\%) and BWS (31\%). Chemotherapy induced reduction in tumor volume was poor in DDS (0.4\% increase) and favorable in BWS (86.9\% reduction). The event-free survival (EFS) of patients with BWS was significantly (p = 0.002) worse than in others. (4) Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.}, language = {en} } @techreport{GesslerSimolaBruns1989, author = {Gessler, Manfred and Simola, Kalle O. and Bruns, Gail A. P.}, title = {Cloning of breakpoints of a chromosome translocation identifies the AN2 locus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30177}, year = {1989}, abstract = {Chromosome translocations involving llpl3 have been associated with familial aniridia in two kindreds highlighting the chromosomal localization of the AN2 locus. This locus is also part of the WAGR complex (Wilros tumor, aniridia, genitourinary abnormalities, and mental retardation). In one kindred, the translocation is associated with a deletion, and probes for this region were used to identify and clone the breakpoints of the translocation in the second kindred. Comparison of phage restriction maps exclude the presence of any sizable deletion in this case. Sequences at the chromosome 11 breakpoint are conserved in multiple species, suggesting that the translocation falls within the AN2 gene.}, language = {en} } @article{SchwarzHameisterGessleretal.1994, author = {Schwarz, Klaus and Hameister, Horst and Gessler, Manfred and Grzeschik, Karl-Heinz and Hansen-Hagge, Thomas E. and Bartram, Claus R.}, title = {Confirmation of the localization of the human recombination activating gene 1 (RAG1) to chromosome 11p13}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59136}, year = {1994}, abstract = {The human recombination activating gene 1 (RAGl) has previously been mapped to chromosomes 14q and 11 p. Here we confirm the chromosome 11 assignment by two independent approaches: autoradiographic and fluorescence in situ hybridization to metaphase spreads and analysis of human-hamster somatic cell hybrid DNA by the polymerase chain reaction (PCR) and Southern blotting. Our results unequivocally localize RAG1 to llp13.}, subject = {Biochemie}, language = {en} } @article{WelterWagnerFurtwaengleretal.2021, author = {Welter, Nils and Wagner, Angelo and Furtw{\"a}ngler, Rhoikos and Melchior, Patrick and Kager, Leo and Vokuhl, Christian and Schenk, Jens-Peter and Meier, Clemens Magnus and Siemer, Stefan and Gessler, Manfred and Graf, Norbert}, title = {Correction: Welter et al. Characteristics of nephroblastoma/nephroblastomatosis in children with a clinically reported underlying malformation or cancer predisposition syndrome. Cancers 2021, 13, 5016}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {22}, issn = {2072-6694}, doi = {10.3390/cancers13225743}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250135}, year = {2021}, abstract = {In the original article [1] there was a mistake in Table 2 as published. Table 2 contains wrong percentages in lines Bilateral disease and Patients with CPS or GU. For this reason the table should be replaced with the correct one as shown below.}, language = {en} } @article{VortkampFranzGessleretal.1992, author = {Vortkamp, Andrea and Franz, Thomas and Gessler, Manfred and Grzeschik, Karl-Heinz}, title = {Deletion of GLI3 supports the homology of the human Greig cephalopolysyndactyly syndrome (GCPS) and the mouse mutant extra toes (Xt)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30166}, year = {1992}, abstract = {No abstract available}, language = {en} } @article{GesslerBarnekow1984, author = {Gessler, Manfred and Barnekow, Angelika}, title = {Differential expression of the cellular oncogenes c-src and c-yes in embryonal and adult chicken tissues}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59289}, year = {1984}, abstract = {The cellular onc-genes c-src and c-yes are expressed very differently during chicken embryonic development. The c-src mRNA and its translational product are detectable at high levels in brain extracts of chicken embryos and adult chickens, whereas muscle extracts show an age-dependent decrease in the amounts of c-src-specific mRNA and pp60c-src kinase activity. In contrast, the Ievels of c-yes mRNA in brain, heart, and muscle are relatively low in early embryonic stages and increase later on to values comparable to those found for liver, while in adult animals the pattern of c-yes expression is similar to that of the c-src gene. From the close correlation between the Ievels of pp60c-src, its enzymatic activity, and its corresponding mRNA at a given stage of development and in given tissues, it appears that the expression of pp60c-src is primarily controlled at the level of transcription. It is suggested that because of the different patterns of expression, the two cellular oncogenes, c-src and c-yes, play different roles in cell proliferation during early embryonic stages as weil as in ensuing differentiation processes.}, subject = {Biochemie}, language = {en} } @article{PoulatMorinKonigetal.1993, author = {Poulat, F. and Morin, D. and Konig, A. and Brun, P. and Giltay, J. and Sultan, C. and Dumas, R. and Gessler, Manfred and Berta, P.}, title = {Distinct molecular origins for Denys-Drash and Frasier syndromes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59172}, year = {1993}, abstract = {The direct involvment of the Wilm's tumor suppressor gene (WTl) in Denys-Drash syndrome through mutations within exons 8 or 9 has recently been established. The absence of such alterations in three patients with Frasier syndrome provides a molecular basis for distinguishing these two syndromes that are associated with streak gonads, pseudohermaphroditism and renal failure.}, subject = {Biochemie}, language = {en} } @article{KonigJakubiczkaWieackeretal.1993, author = {Konig, Anja and Jakubiczka, Sybille and Wieacker, Peter and Schl{\"o}sser, Hans W. and Gessler, Manfred}, title = {Further evidence that imbalance of WT1 isoforms may be involved in Denys-Drash syndrome}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59167}, year = {1993}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{ChagtaiZillDaineseetal.2016, author = {Chagtai, Tasnim and Zill, Christina and Dainese, Linda and Wegert, Jenny and Savola, Suvi and Popov, Sergey and Mifsud, William and Vujanic, Gordan and Sebire, Neil and Le Bouc, Yves and Ambros, Peter F. and Kager, Leo and O`Sullivan, Maureen J. and Blaise, Annick and Bergeron, Christophe and Holmquist Mengelbier, Linda and Gisselsson, David and Kool, Marcel and Tytgat, Godelieve A.M. and van den Heuvel-Eibrink, Marry M. and Graf, Norbert and van Tinteren, Harm and Coulomb, Aurore and Gessler, Manfred and Williams, Richard Dafydd and Pritchard-Jones, Kathy}, title = {Gain of 1q As a Prognostic Biomarker in Wilms Tumors (WTs) Treated With Preoperative Chemotherapy in the International Society of Paediatric Oncology (SIOP) WT 2001 Trial: a SIOP Renal Tumours Biology Consortium Study}, series = {Journal of Clinical Oncology}, volume = {34}, journal = {Journal of Clinical Oncology}, number = {26}, doi = {10.1200/JCO.2015.66.0001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187478}, pages = {3195-3205}, year = {2016}, abstract = {Purpose Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging and histologic assessment of response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, and many successfully treated patients are exposed to treatments with significant risks of late effects. To investigate whether molecular biomarkers could improve risk stratification, we assessed 1q status and other potential copy number biomarkers in a large WT series. Materials and Methods WT nephrectomy samples from 586 SIOP WT 2001 patients were analyzed using a multiplex ligation-dependent probe amplification (MLPA) assay that measured the copy number of 1q and other regions of interest. Results One hundred sixty-seven (28\%) of 586 WTs had 1q gain. Five-year event-free survival (EFS) was 75.0\% in patients with 1q gain (95\% CI, 68.5\% to 82.0\%) and 88.2\% in patients without gain (95\% CI, 85.0\% to 91.4\%). OS was 88.4\% with gain (95\% CI, 83.5\% to 93.6\%) and 94.4\% without gain (95\% CI, 92.1\% to 96.7\%). In univariable analysis, 1q gain was associated with poorer EFS (P<.001; hazard ratio, 2.33) and OS (P=.01; hazard ratio, 2.16). The association of 1q gain with poorer EFS retained significance in multivariable analysis adjusted for 1p and 16q loss, sex, stage, age, and histologic risk group. Gain of 1q remained associated with poorer EFS in tumor subsets limited to either intermediate-risk localized disease or nonanaplastic localized disease. Other notable aberrations associated with poorer EFS included MYCN gain and TP53 loss. Conclusion Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage.}, language = {en} } @article{StefanovicBarnettvanDuijvenbodenetal.2014, author = {Stefanovic, Sonia and Barnett, Phil and van Duijvenboden, Karel and Weber, David and Gessler, Manfred and Christoffels, Vincent M.}, title = {GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development}, series = {Nature Communications}, volume = {5}, journal = {Nature Communications}, number = {3680}, issn = {2041-1723}, doi = {10.1038/ncomms4680}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121437}, year = {2014}, abstract = {The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. Here we assess the transcriptional mechanism underlying this localized differentiation process. We show that atrioventricular canal-specific enhancers are GATA-binding site-dependent and act as switches that repress gene activity in the chambers. We find that atrioventricular canal-specific gene loci are enriched in H3K27ac, a marker of active enhancers, in atrioventricular canal tissue and depleted in H3K27ac in chamber tissue. In the atrioventricular canal, Gata4 activates the enhancers in synergy with Bmp2/Smad signalling, leading to H3K27 acetylation. In contrast, in chambers, Gata4 cooperates with pan-cardiac Hdac1 and Hdac2 and chamber-specific Hey1 and Hey2, leading to H3K27 deacetylation and repression. We conclude that atrioventricular canal-specific enhancers are platforms integrating cardiac transcription factors, broadly active histone modification enzymes and localized co-factors to drive atrioventricular canal-specific gene activity.}, language = {en} } @article{VortkampGesslerGrzeschik1991, author = {Vortkamp, Andrea and Gessler, Manfred and Grzeschik, Karl-Heinz}, title = {GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30100}, year = {1991}, abstract = {No abstract available}, language = {de} } @article{SalatWinklerUrlaubetal.2015, author = {Salat, Daniela and Winkler, Anja and Urlaub, Henning and Gessler, Manfred}, title = {Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {6}, doi = {10.1371/journal.pone.0130288}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125769}, pages = {e0130288}, year = {2015}, abstract = {The Hey protein family, comprising Hey1, Hey2 and HeyL in mammals, conveys Notch signals in many cell types. The helix-loop-helix (HLH) domain as well as the Orange domain, mediate homo- and heterodimerization of these transcription factors. Although distinct interaction partners have been identified so far, their physiological relevance for Hey functions is still largely unclear. Using a tandem affinity purification approach and mass spectrometry analysis we identified members of an ubiquitin E3-ligase complex consisting of FBXO45, PAM and SKP1 as novel Hey1 associated proteins. There is a direct interaction between Hey1 and FBXO45, whereas FBXO45 is needed to mediate indirect Hey1 binding to SKP1. Expression of Hey1 induces translocation of FBXO45 and PAM into the nucleus. Hey1 is a short-lived protein that is degraded by the proteasome, but there is no evidence for FBXO45-dependent ubiquitination of Hey1. On the contrary, Hey1 mediated nuclear translocation of FBXO45 and its associated ubiquitin ligase complex may extend its spectrum to additional nuclear targets triggering their ubiquitination. This suggests a novel mechanism of action for Hey bHLH factors.}, language = {en} } @article{GesslerPoustkaCaveneeetal.1990, author = {Gessler, Manfred and Poustka, Annemarie and Cavenee, Webster and Neve, Rachael L. and Orkin, Stuart H. and Bruns, Gail A.}, title = {Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30122}, year = {1990}, abstract = {No abstract available}, language = {en} }