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 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.
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 - Chagtai, Tasnim
A1 - Zill, Christina
A1 - Dainese, Linda
A1 - Wegert, Jenny
A1 - Savola, Suvi
A1 - Popov, Sergey
A1 - Mifsud, William
A1 - Vujanic, Gordan
A1 - Sebire, Neil
A1 - Le Bouc, Yves
A1 - Ambros, Peter F.
A1 - Kager, Leo
A1 - O`Sullivan, Maureen J.
A1 - Blaise, Annick
A1 - Bergeron, Christophe
A1 - Holmquist Mengelbier, Linda
A1 - Gisselsson, David
A1 - Kool, Marcel
A1 - Tytgat, Godelieve A.M.
A1 - van den Heuvel-Eibrink, Marry M.
A1 - Graf, Norbert
A1 - van Tinteren, Harm
A1 - Coulomb, Aurore
A1 - Gessler, Manfred
A1 - Williams, Richard Dafydd
A1 - Pritchard-Jones, Kathy
T1 - 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
JF - Journal of Clinical Oncology
N2 - 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.
KW - Poor-prognosis
KW - Mutations
KW - Gene
KW - Drosha
KW - MYCN
KW - Mechanisms
KW - Reveals
KW - Event
KW - Relapse
KW - Locus
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187478
VL - 34
IS - 26
ER -
TY - JOUR
A1 - Gessler, Manfred
A1 - Barnekow, Angelika
T1 - Differential expression of the cellular oncogenes c-src and c-yes in embryonal and adult chicken tissues
N2 - 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.
KW - Biochemie
Y1 - 1984
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59289
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 - Gessler, Manfred
A1 - Bruns, Gail A. P.
T1 - Molecular mapping and cloning of the breakpoints of a chromosome 11p14.1-p13 deletion associated with the AGR syndrome
N2 - Chromosome 11p13 is frequently rearranged in individuals with the WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) or parts of this syndrome. To map the cytogenetic aberrations molecularly, we screened DNA from cell Unes with known WAGR-related chromosome abnormalities for rearrangements with pulsed fleld gel (PFG) analysis using probes deleted from one chromosome 11 homolog of a WAGR patient. The first alteration was detected in a cell line from an individual with aniridia, genitourinary anomalies, mental retardation, and a deletion described as 11p14.1-p13. We have located one breakpoint close to probe HU11-164B and we have cloned both breakpoint sites as well as the junctional fragment. The breakpoints subdivide current intervals on the genetic map, and the probes for both sides will serve as important additional markers for a long-range restriction map of this region. Further characterization and sequencing of the breakpoints may yield insight into the mechanisms by which these deletions occur.
KW - Biochemie
Y1 - 1988
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59264
ER -
TY - JOUR
A1 - Gessler, Manfred
A1 - Grupe, Andrew
A1 - Grzeschik, Karl-Heinz
A1 - Pongs, Olaf
T1 - The potassium channel gene HK1 maps to human chromosome 11p14.1, close to the FSHB gene
N2 - Transiently activating (A-type) potassium (K) channels are important regulators of action potential and action potential firing frequencies. HK1 designates the firsthuman cDNA that is highly homologous to the rat RCK4 cDNA that codes for an A-type K-channel. The HK1 channel is expressed in heart. By somatic cell hybrid analysis, the HK1 gene has been assigned to human chromosome 11p13-pl4, the WAGR deletion region (Wilms tumor, aniridia, genito-urinary abnormalities and mental retardation). Subsequent pulsed field gel (PFG) analysis and comparison with the well-established PFG map of this region localized the gene to 11p14, 200-600 kb telomeric to the FSHB gene.
KW - Biochemie
Y1 - 1992
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59184
ER -
TY - JOUR
A1 - Gessler, Manfred
A1 - Hameister, H.
A1 - Henry, I.
A1 - Junien, C.
A1 - Braun, T.
A1 - Arnold, H. H.
T1 - The human MyoD1 (MYF3) gene maps on the short arm of chromosome 11 but is not associated with the WAGR locus or the region for the Beckwith-Wiedemann syndrome
N2 - The human gene encoding the myogenic determination factor myf3 (mouse MyoD1) has been mapped to the short arm of chromosome 11. Analysis of several somatic cell hybrids containing various derivatives with deletions or translocations revealed that the human MyoD (MYF3) gene is not associated with the WAGR locus at chromosomal band 11pl3 nor with the loss of the heterozygosity region at 11p15.5 related to the Beckwith-Wiedemann syndrome. Subregional mapping by in situ hybridization with an myf3 specific probe shows that the gene resides at the chromosomal band llp14, possibly at llp14.3.
KW - Biochemie
Y1 - 1990
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59221
ER -
TY - JOUR
A1 - Gessler, Manfred
A1 - Konig, Anja
A1 - Moore, Jay
A1 - Qualman, Steven
A1 - Arden, Karen
A1 - Cavenee, Webster
A1 - Bruns, Gail
T1 - Homozygous inactivation of WTI in a Wilms' tumor associated with the WAGR syndrome
N2 - Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate II p 13 Wilms' tumor gene, WTI, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome II allele encompassing the WTI gene. Analysis of the remaining WTI allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WTI polypeptide as a transcriptional regulator.
KW - Biochemie
Y1 - 1993
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59146
ER -
TY - JOUR
A1 - Gessler, Manfred
A1 - König, A.
A1 - Arden, K.
A1 - Grundy, P.
A1 - Orkin, S. H.
A1 - Sallan, S.
A1 - Peters, C.
A1 - Ruyle, S.
A1 - Mandell, J.
A1 - Li, F.
A1 - Cavenee, W.
A1 - Bruns, G. A.
T1 - Infrequent mutation of the WT1 gene in 77 Wilms' Tumors
N2 - Homozygous deletions in Wilms' tumor DNA have been a key step in the identification and isolation of the WTI gene. Several additional loci are also postulated to contribute to Wilms' tumor formation. To assess the frequency of WTI alterations we have analyzed the WTI locus in a panel of 77 Wilms' tumors. Eight tumors showed evidence for large deletions of several hundred or thousand kilobasepairs of DNA, some of which were also cytogenetically detected. Additional intragenic mutations were detected using more sensitive SSCP analyses to scan all 10 WTI exons. Most of these result in premature stop codons or missense mutations that inactivate the remaining WTI allele. The overall frequency of WTI alterations detected with these methods is less than 15%. While some mutations may not be detectable with the methods employed, our results suggest that direct alterations of the WTI gene are present in only a small fraction of Wilms' tumors. Thus, mutations at other Wilms' tumor loci or disturbance of interactions between these genes likely play an important role in Wilms' tumor development.
KW - Wilms' tumor
KW - WTI
KW - Zinc finger gene
KW - Tumor suppressor gene
KW - Nephroblastoma
KW - Deletion analysis
KW - SSCP analysis
KW - Mutation screening
Y1 - 1994
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-34308
ER -
TY - JOUR
A1 - Gessler, Manfred
A1 - König, A.
A1 - Bruns, G. A. P.
T1 - The genomic organization and expression of the WT1 gene
N2 - The Wilms tumor gene WTl, a proposed tumor suppressor gene, has been identifled based on its location within a homozygous deletion found in tumor tissue. The gene encodes a putative transcription factor containing a Cys/His zinc finger domain. The critical homozygous deletions, however, are rarely seen, suggesting that in many cases the gene may be inactivated by more subtle alterations. To facilitate the seareh for smaller deletions and point mutations we have established the genomic organization of the WTl gene and have determined the sequence of all 10 exons and flanking intron DNA. The pattern of alternative splicing in two regions has been characterized in detail. These results will form the basis for future studies of mutant alleles at this locus.
KW - Biochemie
Y1 - 1992
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59195
ER -
TY - JOUR
A1 - Gessler, Manfred
A1 - Poustka, Annemarie
A1 - Cavenee, Webster
A1 - Neve, Rachael L.
A1 - Orkin, Stuart H.
A1 - Bruns, Gail A.
T1 - Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping
N2 - No abstract available
Y1 - 1990
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30122
ER -
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 - Gröbner, Susanne N.
A1 - Worst, Barbara C.
A1 - Weischenfeldt, Joachim
A1 - Buchhalter, Ivo
A1 - Kleinheinz, Kortine
A1 - Rudneva, Vasilisa A.
A1 - Johann, Pascal D.
A1 - Balasubramanian, Gnana Prakash
A1 - Segura-Wang, Maia
A1 - Brabetz, Sebastian
A1 - Bender, Sebastian
A1 - Hutter, Barbara
A1 - Sturm, Dominik
A1 - Pfaff, Elke
A1 - Hübschmann, Daniel
A1 - Zipprich, Gideon
A1 - Heinold, Michael
A1 - Eils, Jürgen
A1 - Lawerenz, Christian
A1 - Erkek, Serap
A1 - Lambo, Sander
A1 - Waszak, Sebastian
A1 - Blattmann, Claudia
A1 - Borkhardt, Arndt
A1 - Kuhlen, Michaela
A1 - Eggert, Angelika
A1 - Fulda, Simone
A1 - Gessler, Manfred
A1 - Wegert, Jenny
A1 - Kappler, Roland
A1 - Baumhoer, Daniel
A1 - Stefan, Burdach
A1 - Kirschner-Schwabe, Renate
A1 - Kontny, Udo
A1 - Kulozik, Andreas E.
A1 - Lohmann, Dietmar
A1 - Hettmer, Simone
A1 - Eckert, Cornelia
A1 - Bielack, Stefan
A1 - Nathrath, Michaela
A1 - Niemeyer, Charlotte
A1 - Richter, Günther H.
A1 - Schulte, Johannes
A1 - Siebert, Reiner
A1 - Westermann, Frank
A1 - Molenaar, Jan J.
A1 - Vassal, Gilles
A1 - Witt, Hendrik
A1 - Burkhardt, Birgit
A1 - Kratz, Christian P.
A1 - Witt, Olaf
A1 - van Tilburg, Cornelis M.
A1 - Kramm, Christof M.
A1 - Fleischhack, Gudrun
A1 - Dirksen, Uta
A1 - Rutkowski, Stefan
A1 - Frühwald, Michael
A1 - Hoff, Katja von
A1 - Wolf, Stephan
A1 - Klingebeil, Thomas
A1 - Koscielniak, Ewa
A1 - Landgraf, Pablo
A1 - Koster, Jan
A1 - Resnick, Adam C.
A1 - Zhang, Jinghui
A1 - Liu, Yanling
A1 - Zhou, Xin
A1 - Waanders, Angela J.
A1 - Zwijnenburg, Danny A.
A1 - Raman, Pichai
A1 - Brors, Benedikt
A1 - Weber, Ursula D.
A1 - Northcott, Paul A.
A1 - Pajtler, Kristian W.
A1 - Kool, Marcel
A1 - Piro, Rosario M.
A1 - Korbel, Jan O.
A1 - Schlesner, Matthias
A1 - Eils, Roland
A1 - Jones, David T. W.
A1 - Lichter, Peter
A1 - Chavez, Lukas
A1 - Zapatka, Marc
A1 - Pfister, Stefan M.
T1 - The landscape of genomic alterations across childhood cancers
JF - Nature
N2 - Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
KW - cancer genomics
KW - oncogenesis
KW - paediatric cancer
KW - predictive markers
KW - translational research
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229579
VL - 555
ER -
TY - JOUR
A1 - Heisig, Julia
A1 - Weber, David
A1 - Englberger, Eva
A1 - Winkler, Anja
A1 - Kneitz, Susanne
A1 - Sung, Wing-Kin
A1 - Wolf, Elmar
A1 - Eilers, Martin
A1 - Wei, Chia-Lin
A1 - Gessler, Manfred
T1 - Target Gene Analysis by Microarrays and Chromatin Immunoprecipitation Identifies HEY Proteins as Highly Redundant bHLH Repressors
N2 - HEY bHLH transcription factors have been shown to regulate multiple key steps in cardiovascular development. They can be induced by activated NOTCH receptors, but other upstream stimuli mediated by TGFß and BMP receptors may elicit a similar response. While the basic and helix-loop-helix domains exhibit strong similarity, large parts of the proteins are still unique and may serve divergent functions. The striking overlap of cardiac defects in HEY2 and combined HEY1/HEYL knockout mice suggested that all three HEY genes fulfill overlapping function in target cells. We therefore sought to identify target genes for HEY proteins by microarray expression and ChIPseq analyses in HEK293 cells, cardiomyocytes, and murine hearts. HEY proteins were found to modulate expression of their target gene to a rather limited extent, but with striking functional interchangeability between HEY factors. Chromatin immunoprecipitation revealed a much greater number of potential binding sites that again largely overlap between HEY factors. Binding sites are clustered in the proximal promoter region especially of transcriptional regulators or developmental control genes. Multiple lines of evidence suggest that HEY proteins primarily act as direct transcriptional repressors, while gene activation seems to be due to secondary or indirect effects. Mutagenesis of putative DNA binding residues supports the notion of direct DNA binding. While class B E-box sequences (CACGYG) clearly represent preferred target sequences, there must be additional and more loosely defined modes of DNA binding since many of the target promoters that are efficiently bound by HEY proteins do not contain an Ebox motif. These data clearly establish the three HEY bHLH factors as highly redundant transcriptional repressors in vitro and in vivo, which explains the combinatorial action observed in different tissues with overlapping expression.
KW - Biologie
Y1 - 2012
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75341
ER -
TY - JOUR
A1 - Henry, Isabelle
A1 - Hoovers, Jan
A1 - Barichard, Fernande
A1 - Berthéas, Marie-Francoise
A1 - Puech, Anne
A1 - Prieur, Fabienne
A1 - Gessler, Manfred
A1 - Bruns, Gail
A1 - Mannens, Marcel
A1 - Junien, Claudine
T1 - Pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in a family
N2 - The combined use of qualitative and quantitative analysis of I I p I 3 polymorphic markers tagether with chromosomal in situ suppression hybridization (CISS) with biotin labeled probes mapping to I I p allowed us to characterize a complex rearrangement segregating in a family. We detected a pericentric intrachromosomal insertion responsible (or recurrence of del( I I )(p 13p 14) in the family: an insertion of band I I p 13-p 14 carrying the genes for predisposition to Wilms' tumor, WT I, and for aniridia, AN2, into the long arm of chromosome I I in II q 13-q 1<4. Asymptomatic balanced carriers were observed over three generations. Classical cytogenetics had failed to detect this anomaly in the balanced carriers, who were first considered to be somatic mosaics for del( II )(p 13). Two of these women gave birth to children carrying a deleted chromosome II. most likely resulting from the loss of the I I p 13 band inserted in I I q. Although in both cases the deletion encompassed exactly the same maternally inherited markers, there was a wide Variation in clinical expression. One child, with the karyotype 46,XY,del(ll)(pllpl4), presented the full-blown WAGR syndrome with anlridia, mental retardation, Wilms' tumor, and pseudohermaphroditism, but also had proteinuria and glomerular sclerosis reminiscent of Drash syndrome. In contrast, the other one, a girl with the karyotype 46,XX,del( I I )(p I 3), only had aniridia. Although a specific set of mutational sites has been observed in Drash patients, these findings suggest that the loss of one copy of the WTI gene can result in similar genital and kidney abnormalities.
KW - Biochemie
Y1 - 1993
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59157
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 - Konig, Anja
A1 - Jakubiczka, Sybille
A1 - Wieacker, Peter
A1 - Schlösser, Hans W.
A1 - Gessler, Manfred
T1 - Further evidence that imbalance of WT1 isoforms may be involved in Denys-Drash syndrome
N2 - No abstract available
KW - Biochemie
Y1 - 1993
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59167
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 -
TY - JOUR
A1 - Martín, Ovidio Jiménez
A1 - Schlosser, Andreas
A1 - Furtwängler, Rhoikos
A1 - Wegert, Jenny
A1 - Gessler, Manfred
T1 - MYCN and MAX alterations in Wilms tumor and identification of novel N-MYC interaction partners as biomarker candidates
JF - Cancer Cell International
N2 - Background
Wilms tumor (WT) is the most common renal tumor in childhood. Among others, MYCN copy number gain and MYCN P44L and MAX R60Q mutations have been identified in WT. MYCN encodes a transcription factor that requires dimerization with MAX to activate transcription of numerous target genes. MYCN gain has been associated with adverse prognosis in different childhood tumors including WT. The MYCN P44L and MAX R60Q mutations, located in either the transactivating or basic helix-loop-helix domain, respectively, are predicted to be damaging by different pathogenicity prediction tools, but the functional consequences remain to be characterized.
Methods
We screened a large cohort of unselected WTs for MYCN and MAX alterations. Wild-type and mutant protein function were characterized biochemically, and we analyzed the N-MYC protein interactome by mass spectrometric analysis of N-MYC containing protein complexes.
Results
Mutation screening revealed mutation frequencies of 3% for MYCN P44L and 0.9% for MAX R60Q that are associated with a higher risk of relapse. Biochemical characterization identified a reduced transcriptional activation potential for MAX R60Q, while the MYCN P44L mutation did not change activation potential or protein stability. The protein interactome of N-MYC-P44L was likewise not altered as shown by mass spectrometric analyses of purified N-MYC complexes. Nevertheless, we could identify a number of novel N-MYC partner proteins, e.g. PEG10, YEATS2, FOXK1, CBLL1 and MCRS1, whose expression is correlated with MYCN in WT samples and several of these are known for their own oncogenic potential.
Conclusions
The strongly elevated risk of relapse associated with mutant MYCN and MAX or elevated MYCN expression corroborates their role in WT oncogenesis. Together with the newly identified co-expressed interactors they expand the range of potential biomarkers for WT stratification and targeting, especially for high-risk WT.
KW - Wilms tumor
KW - MYCN
KW - MAX
KW - interactome
KW - mutation screening
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265542
VL - 21
ER -
TY - JOUR
A1 - Poulat, F.
A1 - Morin, D.
A1 - Konig, A.
A1 - Brun, P.
A1 - Giltay, J.
A1 - Sultan, C.
A1 - Dumas, R.
A1 - Gessler, Manfred
A1 - Berta, P.
T1 - Distinct molecular origins for Denys-Drash and Frasier syndromes
N2 - 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.
KW - Biochemie
Y1 - 1993
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59172
ER -