TY  - JOUR
A1  - Gessler, Manfred
A1  - Thomas, G. H.
A1  - Couillin, P.
A1  - Junien, C.
A1  - McGillivray, B. C.
A1  - Hayden, M.
A1  - Jaschek, G.
A1  - Bruns, G. A.
T1  - A deletion map of the WAGR region on chromosome II
N2  - 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.
KW  - Biochemie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59255
ER  - 
TY  - JOUR
A1  - Gessler, Manfred
A1  - Bruns, G. A. P.
T1  - A physical map around the WAGR complex on the short arm of chromosome 11
N2  - 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.
KW  - Biochemie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59246
ER  - 
TY  - JOUR
A1  - Vortkamp, A.
A1  - Thias, U.
A1  - Gessler, Manfred
A1  - Rosenkranz, W.
A1  - Kroisel, P. M.
A1  - Tommerup, N.
A1  - Kruger, G.
A1  - Gotz, J.
A1  - Pelz, L.
A1  - Grzeschik, Karl-Heinz
T1  - A somatic cell hybrid panel and DNA probes for physical mapping of human chromosome 7p
N2  - No abstract available
KW  - Biochemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59217
ER  - 
TY  - JOUR
A1  - Schwartz, Faina
A1  - Neve, Rachel
A1  - Eisenman, Robert
A1  - Gessler, Manfred
A1  - Bruns, Gail
T1  - A WAGR region gene between PAX-6 and FSHB expressed in fetal brain
N2  - 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.
KW  - Biochemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59125
ER  - 
TY  - JOUR
A1  - Barnekow, Angelika
A1  - Gessler, Manfred
T1  - Activation of the pp60\(^{c-src}\) kinase during differentiation of monomyelocytic cells in vitro
N2  - 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 pp60<sup>c-src</sup> tyrosine kinase, but not with increased c-src gene expression. Control experiments exclude an interaction of TPA and DMSO themselves with the pp60<sup>c-src</sup> kinase.
KW  - Biochemie
KW  - c-src
KW  - differentiation
KW  - protein tyrosine kinase
KW  - protooncogene
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59278
ER  - 
TY  - JOUR
A1  - Segerer, Gabriela
A1  - Hadamek, Kerstin
A1  - Zundler, Matthias
A1  - Fekete, Agnes
A1  - Seifried, Annegrit
A1  - Mueller, Martin J.
A1  - Koentgen, Frank
A1  - Gessler, Manfred
A1  - Jeanclos, Elisabeth
A1  - Gohla, Antje
T1  - An essential developmental function for murine phosphoglycolate phosphatase in safeguarding cell proliferation
JF  - Scientific Reports
N2  - Mammalian phosphoglycolate phosphatase (PGP) is thought to target phosphoglycolate, a 2-deoxyribose fragment derived from the repair of oxidative DNA lesions. However, the physiological role of this activity and the biological function of the DNA damage product phosphoglycolate is unknown. We now show that knockin replacement of murine Pgp with its phosphatase-inactive Pgp\(^{D34N}\) mutant is embryonically lethal due to intrauterine growth arrest and developmental delay in midgestation. PGP inactivation attenuated triosephosphate isomerase activity, increased triglyceride levels at the expense of the cellular phosphatidylcholine content, and inhibited cell proliferation. These effects were prevented under hypoxic conditions or by blocking phosphoglycolate release from damaged DNA. Thus, PGP is essential to sustain cell proliferation in the presence of oxygen. Collectively, our findings reveal a previously unknown mechanism coupling a DNA damage repair product to the control of intermediary metabolism and cell proliferation.
KW  - cell proliferation
KW  - DNA metabolism
KW  - lipidomics
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181094
VL  - 6
ER  - 
TY  - JOUR
A1  - Higgins, M. J.
A1  - Smilinich, N. J.
A1  - Sait, S.
A1  - Koenig, A.
A1  - Pongratz, J.
A1  - Gessler, Manfred
A1  - Richard III., C. W.
A1  - James, M. R.
A1  - Sanford, J. P.
A1  - Kim, B.-W.
A1  - Cattelane, J.
A1  - Nowak, N. J.
A1  - Winterpacht, A.
A1  - Zabel, B. U.
A1  - Munroe, D. J.
A1  - Bric, E.
A1  - Housman, D. E.
A1  - Jones, C.
A1  - Nakamura, Y.
A1  - Gerhard, D. S.
A1  - Shows, T. B.
T1  - An Ordered NotI Fragment Map of Human Chromosome Band 11p15
N2  - 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.
KW  - Genom / Genkartierung / Genanalyse
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-45766
ER  - 
TY  - JOUR
A1  - Schmitt, Jana
A1  - Keller, Andreas
A1  - Nourkami-Tutdibi, Nasenien
A1  - Heisel, Sabrina
A1  - Habel, Nunja
A1  - Leidinger, Petra
A1  - Ludwig, Nicole
A1  - Gessler, Manfred
A1  - Graf, Norbert
A1  - Berthold, Frank
A1  - Lenhof, Hans-Peter
A1  - Meese, Eckart
T1  - Autoantibody Signature Differentiates Wilms Tumor Patients from Neuroblastoma Patients
JF  - PLoS ONE
N2  - 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.
KW  - Heparan-sulfate
KW  - N-Myc
KW  - Serum autoantibodies
KW  - Suppressors EXT1
KW  - Neuro-blastoma
KW  - Allelic loss
KW  - Lung-cancer
KW  - Children
KW  - Amplification
KW  - Therapy
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133794
VL  - 6
IS  - 12
ER  - 
TY  - JOUR
A1  - Welter, Nils
A1  - Wagner, Angelo
A1  - Furtwängler, Rhoikos
A1  - Melchior, Patrick
A1  - Kager, Leo
A1  - Vokuhl, Christian
A1  - Schenk, Jens-Peter
A1  - Meier, Clemens Magnus
A1  - Siemer, Stefan
A1  - Gessler, Manfred
A1  - Graf, Norbert
T1  - Characteristics of nephroblastoma/nephroblastomatosis in children with a clinically reported underlying malformation or cancer predisposition syndrome
JF  - Cancers
N2  - (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.
KW  - nephroblastoma
KW  - clinical malformations
KW  - cancer predisposition syndromes
KW  - tumor surveillance
KW  - outcome
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248434
SN  - 2072-6694
VL  - 13
IS  - 19
ER  - 
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  -