Schildhaus, Hans-Ulrich

[["dc.bibliographiccitation.firstpage","10577"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","10585"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Scheffler, Matthias"],["dc.contributor.author","Schultheis, Anne"],["dc.contributor.author","Teixido, Cristina"],["dc.contributor.author","Michels, Sebastian"],["dc.contributor.author","Morales-Espinosa, Daniela"],["dc.contributor.author","Viteri, Santiago"],["dc.contributor.author","Hartmann, Wolfgang"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Fischer, Rieke"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","Sebastian, Martin"],["dc.contributor.author","Serke, Monika"],["dc.contributor.author","Kaminsky, Britta"],["dc.contributor.author","Randerath, Winfried"],["dc.contributor.author","Gerigk, Ulrich"],["dc.contributor.author","Ko, Yon-Dschun"],["dc.contributor.author","Krüger, Stefan"],["dc.contributor.author","Schnell, Roland"],["dc.contributor.author","Rothe, Achim"],["dc.contributor.author","Kropf-Sanchen, Cornelia"],["dc.contributor.author","Heukamp, Lukas"],["dc.contributor.author","Rosell, Rafael"],["dc.contributor.author","Büttner, Reinhard"],["dc.contributor.author","Wolf, Jürgen"],["dc.date.accessioned","2019-07-09T11:42:39Z"],["dc.date.available","2019-07-09T11:42:39Z"],["dc.date.issued","2015-04-30"],["dc.description.abstract","BACKGROUND: While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. PATIENTS AND METHODS: 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. RESULTS: 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations. CONCLUSION: ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC."],["dc.identifier.doi","10.18632/oncotarget.3387"],["dc.identifier.fs","611826"],["dc.identifier.pmid","25868855"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13617"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58716"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.mesh","Adenocarcinoma"],["dc.subject.mesh","Adult"],["dc.subject.mesh","Aged"],["dc.subject.mesh","Female"],["dc.subject.mesh","Gene Rearrangement"],["dc.subject.mesh","Genetic Variation"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Lung Neoplasms"],["dc.subject.mesh","Male"],["dc.subject.mesh","Middle Aged"],["dc.subject.mesh","Prognosis"],["dc.subject.mesh","Protein-Tyrosine Kinases"],["dc.subject.mesh","Proto-Oncogene Proteins"],["dc.subject.mesh","Survival Analysis"],["dc.subject.mesh","Treatment Outcome"],["dc.title","ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","13"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Cancer"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Ihle, Michaela A."],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","König, Katharina"],["dc.contributor.author","Grünewald, Inga"],["dc.contributor.author","Schlaak, Max"],["dc.contributor.author","Kreuzberg, Nicole"],["dc.contributor.author","Tietze, Lothar"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Büttner, Reinhard"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.date.accessioned","2019-07-09T11:39:42Z"],["dc.date.available","2019-07-09T11:39:42Z"],["dc.date.issued","2014"],["dc.description.abstract","Background The approval of vemurafenib in the US 2011 and in Europe 2012 improved the therapy of not resectable or metastatic melanoma. Patients carrying a substitution of valine to glutamic acid at codon 600 (p.V600E) or a substitution of valine to leucine (p.V600K) in BRAF show complete or partial response. Therefore, the precise identification of the underlying somatic mutations is essential. Herein, we evaluate the sensitivity, specificity and feasibility of six different methods for the detection of BRAF mutations. Methods Samples harboring p.V600E mutations as well as rare mutations in BRAF exon 15 were compared to wildtype samples. DNA was extracted from formalin-fixed paraffin-embedded tissues by manual micro-dissection and automated extraction. BRAF mutational analysis was carried out by high resolution melting (HRM) analysis, pyrosequencing, allele specific PCR, next generation sequencing (NGS) and immunohistochemistry (IHC). All mutations were independently reassessed by Sanger sequencing. Due to the limited tumor tissue available different numbers of samples were analyzed with each method (82, 72, 60, 72, 49 and 82 respectively). Results There was no difference in sensitivity between the HRM analysis and Sanger sequencing (98%). All mutations down to 6.6% allele frequency could be detected with 100% specificity. In contrast, pyrosequencing detected 100% of the mutations down to 5% allele frequency but exhibited only 90% specificity. The allele specific PCR failed to detect 16.3% of the mutations eligible for therapy with vemurafenib. NGS could analyze 100% of the cases with 100% specificity but exhibited 97.5% sensitivity. IHC showed once cross-reactivity with p.V600R but was a good amendment to HRM. Conclusion Therefore, at present, a combination of HRM and IHC is recommended to increase sensitivity and specificity for routine diagnostic to fulfill the European requirements concerning vemurafenib therapy of melanoma patients."],["dc.identifier.doi","10.1186/1471-2407-14-13"],["dc.identifier.fs","603375"],["dc.identifier.pmid","24410877"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10053"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58025"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Comparison of high resolution melting analysis, pyrosequencing, next generation sequencing and immunohistochemistry to conventional Sanger sequencing for the detection of p.V600E and non-p.V600E BRAF mutations"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","20215"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","20130"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Künstlinger, Helen"],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Brors, Benedikt"],["dc.contributor.author","Heydt, Carina"],["dc.contributor.author","Ihle, Michaela Angelika"],["dc.contributor.author","Mechtersheimer, Gunhild"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Büttner, Reinhard"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.date.accessioned","2019-07-09T11:42:38Z"],["dc.date.available","2019-07-09T11:42:38Z"],["dc.date.issued","2015-08-21"],["dc.description.abstract","Myxoid liposarcomas account for more than one third of liposarcomas and about 10% of all adult soft tissue sarcomas. The tumors are characterized by specific chromosomal translocations leading to the chimeric oncogenes FUS-DDIT3 or EWS1R-DDIT3. The encoded fusion proteins act as aberrant transcription factors. Therefore, we implemented comparative expression analyses using whole-genome microarrays in tumor and fat tissue samples. We aimed at identifying differentially expressed genes which may serve as diagnostic or prognostic biomarkers or as therapeutic targets. Microarray analyses revealed overexpression of FGFR2 and other members of the FGF/FGFR family. Overexpression of FGFR2 was validated by qPCR, immunohistochemistry and western blot analysis in primary tumor samples. Treatment of the myxoid liposarcoma cell lines MLS 402 and MLS 1765 with the FGFR inhibitors PD173074, TKI258 (dovitinib) and BGJ398 as well as specific siRNAs reduced cell proliferation, induced apoptosis and delayed cell migration. Combination of FGFR inhibitors with trabectedin further increased the effect. Our study demonstrates overexpression of FGFR2 and a functional role of FGFR signaling in myxoid liposarcoma. As FGFR inhibition showed effects on proliferation and cell migration and induced apoptosis in vitro, our data indicate the potential use of FGFR inhibitors as a targeted therapy for these tumors."],["dc.identifier.doi","10.18632/oncotarget.4046"],["dc.identifier.fs","617613"],["dc.identifier.pmid","26036639"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13611"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58712"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Cell Movement"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Cohort Studies"],["dc.subject.mesh","Gene Expression"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Liposarcoma, Myxoid"],["dc.subject.mesh","Microarray Analysis"],["dc.subject.mesh","Pyrimidines"],["dc.subject.mesh","Receptor, Fibroblast Growth Factor, Type 2"],["dc.subject.mesh","Receptors, Fibroblast Growth Factor"],["dc.subject.mesh","Signal Transduction"],["dc.title","FGFR2 is overexpressed in myxoid liposarcoma and inhibition of FGFR signaling impairs tumor growth in vitro."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","122"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Thoracic Oncology"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Michels, Sebastian"],["dc.contributor.author","Scheel, Andreas Hans Joachim"],["dc.contributor.author","Scheffler, Matthias"],["dc.contributor.author","Schultheis, Anne Maria"],["dc.contributor.author","Gautschi, Oliver Pascal"],["dc.contributor.author","Aebersold, Franziska"],["dc.contributor.author","Diebold, Joachim"],["dc.contributor.author","Pall, Georg"],["dc.contributor.author","Rothschild, Sacha"],["dc.contributor.author","Bubendorf, Lukas"],["dc.contributor.author","Hartmann, Wolfgang"],["dc.contributor.author","Heukamp, Lukas Carl"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","Ihle, Michaela Angelika"],["dc.contributor.author","Kuenstlinger, Helen"],["dc.contributor.author","Heydt, Carina"],["dc.contributor.author","Fischer, Rieke N."],["dc.contributor.author","Nogova, Lucia"],["dc.contributor.author","Mattonet, Christian"],["dc.contributor.author","Hein, Rebecca"],["dc.contributor.author","Adams, Anne"],["dc.contributor.author","Gerigk, Ulrich"],["dc.contributor.author","Schulte, Wolfgang"],["dc.contributor.author","Lueders, Heike"],["dc.contributor.author","Grohe, Christian"],["dc.contributor.author","Graeven, Ullrich"],["dc.contributor.author","Mueller-Naendrup, Clemens"],["dc.contributor.author","Draube, Andreas"],["dc.contributor.author","Kambartel, Karl-Otto"],["dc.contributor.author","Krüger, Stefan"],["dc.contributor.author","Schulze-Olden, Susanne"],["dc.contributor.author","Serke, Monika"],["dc.contributor.author","Engel-Riedel, Walburga"],["dc.contributor.author","Kaminsky, Britta"],["dc.contributor.author","Randerath, Winfried J."],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Wolf, Juergen"],["dc.date.accessioned","2018-11-07T10:20:42Z"],["dc.date.available","2018-11-07T10:20:42Z"],["dc.date.issued","2016"],["dc.description.abstract","Introduction: Rearrangements of RET are rare oncogenic events in patients with non-small cell lung cancer (NSCLC). While the characterization of Asian patients suggests a predominance of nonsmokers of young age in this genetically defined lung cancer subgroup, little is known about the characteristics of non-Asian patients. We present the results of an analysis of a European cohort of patients with RET rearranged NSCLC. Methods: Nine hundred ninety-seven patients with KRAS/EGFR/ALK wildtype lung adenocarcinomas were analyzed using fluorescence in situ hybridization for RET fusions. Tumor specimens were molecularly profiled and clinicopathological characteristics of the patients were collected. Results: Rearrangements of RET were identified in 22 patients, with a prevalence of 2.2% in the KRAS/EGFR/ALK wildtype subgroup. Co-occurring genetic aberrations were detected in 10 patients, and the majority had mutations in TP53. The median age at diagnosis was 62 years (range, 39-80 years; mean +/- SD, 61 +/- 11.7 years) with a higher proportion of men (59% versus 41%). There was only a slight predominance of nonsmokers (54.5%) compared to current or former smokers (45.5%). Conclusions: Patients with RET rearranged adenocarcinomas represent a rare and heterogeneous NSCLC sub-group. In some contrast to published data, we see a high prevalence of current and former smokers in our white RET cohort. The significance of co-occurring aberrations, so far, is unclear. (C) 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.jtho.2015.09.016"],["dc.identifier.isi","000373094200014"],["dc.identifier.pmid","26762747"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41941"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1556-1380"],["dc.relation.issn","1556-0864"],["dc.title","Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","UNSP e0120079"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schmitz, Katja"],["dc.contributor.author","Koeppen, Hartmut"],["dc.contributor.author","Binot, Elke"],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","Kuenstlinger, Helen"],["dc.contributor.author","Ihle, Michaela Angelika"],["dc.contributor.author","Heydt, Carina"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Rueschoff, Josef"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.date.accessioned","2018-11-07T09:58:38Z"],["dc.date.available","2018-11-07T09:58:38Z"],["dc.date.issued","2015"],["dc.description.abstract","Soft tissue sarcomas are a heterogeneous group of tumors with many different subtypes. In 2014 an estimated 12,020 newly diagnosed cases and 4,740 soft tissue sarcoma related deaths can be expected in the United States. Many soft tissue sarcomas are associated with poor prognosis and therapeutic options are often limited. The evolution of precision medicine has not yet fully reached the clinical treatment of sarcomas since therapeutically tractable genetic changes have not been comprehensively studied so far. We analyzed a total of 484 adult-type malignant mesenchymal tumors by MET fluorescence in situ hybridization and MET and hepatocyte growth factor immunohistochemistry. Eleven different entities were included, among them the most common and clinically relevant subtypes and tumors with specific translocations or complex genetic changes. MET protein expression was observed in 2.6% of the cases, all of which were either undifferentiated pleomorphic sarcomas or angiosarcomas, showing positivity rates of 14% and 17%, respectively. 6% of the tumors showed hepatocyte growth factor overexpression, mainly seen in undifferentiated pleomorphic sarcomas and angiosarcomas, but also in clear cell sarcomas, malignant peripheral nerve sheath tumors, leiomyosarcomas and gastrointestinal stromal tumors. MET and hepatocyte growth factor overexpression were significantly correlated and may suggest an autocrine activation in these tumors. MET FISH amplification and copy number gain were present in 4% of the tumors (15/413). Two samples, both undifferentiated pleomorphic sarcomas, fulfilled the criteria for high level amplification of MET, one undifferentiated pleomorphic sarcoma reached an intermediate level copy number gain, and 12 samples of different subtypes were categorized as low level copy number gains for MET. Our findings indicate that angiosarcomas and undifferentiated pleomorphic sarcomas rather than other frequent adult-type sarcomas should be enrolled in screening programs for clinical trials with MET inhibitors. The screening methods should include both in situ hybridization and immunohistochemistry."],["dc.description.sponsorship","German Cancer Aid (Deutsche Krebshilfe)"],["dc.identifier.doi","10.1371/journal.pone.0120079"],["dc.identifier.isi","000352475700002"],["dc.identifier.pmid","25844809"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11760"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37407"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","MET Gene Copy Number Alterations and Expression of MET and Hepatocyte Growth Factor Are Potential Biomarkers in Angiosarcomas and Undifferentiated Pleomorphic Sarcomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","907"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical Cancer Research"],["dc.bibliographiccitation.lastpage","915"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Schultheis, Anne Maria"],["dc.contributor.author","Rüschoff, Josef R."],["dc.contributor.author","Binot, Elke"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","Schulte, Wolfgang"],["dc.contributor.author","Ko, Yon-Dschun"],["dc.contributor.author","Schlesinger, Andreas"],["dc.contributor.author","Bos, Marc"],["dc.contributor.author","Gardizi, Masyar"],["dc.contributor.author","Engel-Riedel, Walburga"],["dc.contributor.author","Brockmann, Michael"],["dc.contributor.author","Serke, Monika Heidi"],["dc.contributor.author","Gerigk, Ulrich"],["dc.contributor.author","Hekmat, Khosro"],["dc.contributor.author","Frank, Konrad F."],["dc.contributor.author","Reiser, Marcel"],["dc.contributor.author","Schulz, Holger"],["dc.contributor.author","Krüger, Stefan"],["dc.contributor.author","Stoelben, Erich"],["dc.contributor.author","Zander, Thomas"],["dc.contributor.author","Wolf, Jürgen"],["dc.contributor.author","Buettner, Reinhard"],["dc.date.accessioned","2018-11-07T10:00:53Z"],["dc.date.available","2018-11-07T10:00:53Z"],["dc.date.issued","2015"],["dc.description.abstract","Purpose: MET is a potential therapeutic target in lung cancer and both MET tyrosine kinase inhibitors and monoclonal antibodies have entered clinical trials. MET signaling can be activated by various mechanisms, including gene amplification. In this study, we aimed to investigate MET amplification status in adeno- and squamous cell carcinomas of the lung. We propose clearly defined amplification scores and provide epidemiologic data on MET amplification in lung cancer. Experimental Design: We evaluated the prevalence of increased MET gene copy numbers in 693 treatment-naive cancers by FISH, defined clear cutoff criteria, and correlated FISH results to MET IHC. Results: Two thirds (67%) of lung cancers do not have gains in MET gene copy numbers, whereas 3% show a clear-cut high-level amplification (MET/centromer7 ratio =2.0 or average gene copy number per nucleus =6.0 or =10% of tumor cells containing =15 MET copies). The remaining cases can be subdivided into intermediate- (6%) and low-level gains (24%). Importantly, MET amplifications occur at equal frequencies in squamous and adenocarcinomas without or with EGFR or KRAS mutations. Conclusion: MET amplification is not a mutually exclusive genetic event in therapy-naive non-small cell lung cancer. Our data suggest that it might be useful to determine MET amplification (i) before EGFR inhibitor treatment to identify possible primary resistance to anti-EGFR treatment, and (ii) to select cases that harbor KRAS mutations additionally to MET amplification and, thus, may not benefit from MET inhibition. Furthermore, our study provides comprehensive epidemiologic data for upcoming trials with various MET inhibitors. (C) 2014 AACR."],["dc.identifier.doi","10.1158/1078-0432.CCR-14-0450"],["dc.identifier.isi","000349851200029"],["dc.identifier.pmid","25492085"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37902"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","1557-3265"],["dc.relation.issn","1078-0432"],["dc.title","MET Amplification Status in Therapy-Naive Adeno- and Squamous Cell Carcinomas of the Lung"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1266"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Journal of Thoracic Oncology"],["dc.bibliographiccitation.lastpage","1276"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Michels, Sebastian"],["dc.contributor.author","Massutí, Bartomeu"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Franklin, Jeremy"],["dc.contributor.author","Sebastian, Martin"],["dc.contributor.author","Felip, Enriqueta"],["dc.contributor.author","Grohé, Christian"],["dc.contributor.author","Rodriguez-Abreu, Delvys"],["dc.contributor.author","Abdulla, Diana S.Y."],["dc.contributor.author","Bischoff, Helge"],["dc.contributor.author","Brandts, Christian"],["dc.contributor.author","Carcereny, Enric"],["dc.contributor.author","Corral, Jesús"],["dc.contributor.author","Dingemans, Anne-Marie C."],["dc.contributor.author","Pereira, Eva"],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","Fischer, Rieke N."],["dc.contributor.author","Gardizi, Masyar"],["dc.contributor.author","Heukamp, Lukas"],["dc.contributor.author","Insa, Amelia"],["dc.contributor.author","Kron, Anna"],["dc.contributor.author","Menon, Roopika"],["dc.contributor.author","Persigehl, Thorsten"],["dc.contributor.author","Reck, Martin"],["dc.contributor.author","Riedel, Richard"],["dc.contributor.author","Rothschild, Sacha I."],["dc.contributor.author","Scheel, Andreas H."],["dc.contributor.author","Scheffler, Matthias"],["dc.contributor.author","Schmalz, Petra"],["dc.contributor.author","Smit, Egbert F."],["dc.contributor.author","Limburg, Meike"],["dc.contributor.author","Provencio, Mariano"],["dc.contributor.author","Karachaliou, Niki"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Hellmich, Martin"],["dc.contributor.author","Nogova, Lucia"],["dc.contributor.author","Büttner, Reinhard"],["dc.contributor.author","Rosell, Rafael"],["dc.contributor.author","Wolf, Jürgen"],["dc.date.accessioned","2020-12-10T15:20:07Z"],["dc.date.available","2020-12-10T15:20:07Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.jtho.2019.03.020"],["dc.identifier.issn","1556-0864"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72563"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4837"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Clinical Cancer Research"],["dc.bibliographiccitation.lastpage","4847"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Ortiz-Cuaran, Sandra"],["dc.contributor.author","Scheffler, Matthias"],["dc.contributor.author","Plenker, Dennis"],["dc.contributor.author","Dahmen, Ilona"],["dc.contributor.author","Scheel, Andreas Hans"],["dc.contributor.author","Fernandez-Cuesta, Lynnette"],["dc.contributor.author","Meder, Lydia"],["dc.contributor.author","Lovly, Christine M."],["dc.contributor.author","Persigehl, Thorsten"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Bos, Marc"],["dc.contributor.author","Michels, Sebastian"],["dc.contributor.author","Fischer, Rieke N."],["dc.contributor.author","Albus, Kerstin"],["dc.contributor.author","Koenig, Katharina"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","Ihle, Michaela Angelika"],["dc.contributor.author","PasternackO, Helen"],["dc.contributor.author","Heydt, Carina"],["dc.contributor.author","Becker, Christian"],["dc.contributor.author","Altmueller, Janine"],["dc.contributor.author","Ji, Hongbin"],["dc.contributor.author","Mueller, Christian"],["dc.contributor.author","Florin, Alexandra"],["dc.contributor.author","Heuckmann, Johannes M."],["dc.contributor.author","Nuernberg, Peter"],["dc.contributor.author","Ansen, Sascha"],["dc.contributor.author","Heukamp, Lukas Carl"],["dc.contributor.author","Berg, Johannes"],["dc.contributor.author","Pao, William"],["dc.contributor.author","Peifer, Martin"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Wolfe, Juergen"],["dc.contributor.author","Thomas, Roman K."],["dc.contributor.author","Sos, Martin L."],["dc.date.accessioned","2018-11-07T10:07:47Z"],["dc.date.available","2018-11-07T10:07:47Z"],["dc.date.issued","2016"],["dc.description.abstract","Purpose: To identify novel mechanisms of resistance to third-generation EGFR inhibitors in patients with lung adenocarcinoma that progressed under therapy with either AZD9291 or rociletinib (CO-1686). Experimental Design: We analyzed tumor biopsies from seven patients obtained before, during, and/or after treatment with AZD9291 or rociletinib (CO-1686). Targeted sequencing and FISH analyses were performed, and the relevance of candidate genes was functionally assessed in in vitro models. Results: We found recurrent amplification of either MET or ERBB2 in tumors that were resistant or developed resistance to third-generation EGFR inhibitors and show that ERBB2 and MET activation can confer resistance to these compounds. Furthermore, we identified a KRAS(G12S) mutation in a patient with acquired resistance to AZD9291 as a potential driver of acquired resistance. Finally, we show that dual inhibition of EGFR/MEK might be a viable strategy to overcome resistance in EGFR-mutant cells expressing mutant KRAS. Conclusions: Our data suggest that heterogeneous mechanisms of resistance can drive primary and acquired resistance to third-generation EGFR inhibitors and provide a rationale for potential combination strategies. (C) 2016 AACR."],["dc.identifier.doi","10.1158/1078-0432.CCR-15-1915"],["dc.identifier.eissn","1557-3265"],["dc.identifier.isi","000385630500011"],["dc.identifier.issn","1078-0432"],["dc.identifier.pmid","27252416"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39347"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","1557-3265"],["dc.relation.issn","1078-0432"],["dc.title","Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e104566"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Heydt, Carina"],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","Kuenstlinger, Helen"],["dc.contributor.author","Ihle, Michaela Angelika"],["dc.contributor.author","Koenig, Katharina"],["dc.contributor.author","Heukamp, Lukas Carl"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Odenthal, Margarete"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.date.accessioned","2018-11-07T09:36:42Z"],["dc.date.available","2018-11-07T09:36:42Z"],["dc.date.issued","2014"],["dc.description.abstract","Over the last years, massively parallel sequencing has rapidly evolved and has now transitioned into molecular pathology routine laboratories. It is an attractive platform for analysing multiple genes at the same time with very little input material. Therefore, the need for high quality DNA obtained from automated DNA extraction systems has increased, especially to those laboratories which are dealing with formalin-fixed paraffin-embedded (FFPE) material and high sample throughput. This study evaluated five automated FFPE DNA extraction systems as well as five DNA quantification systems using the three most common techniques, UV spectrophotometry, fluorescent dye-based quantification and quantitative PCR, on 26 FFPE tissue samples. Additionally, the effects on downstream applications were analysed to find the most suitable pre-analytical methods for massively parallel sequencing in routine diagnostics. The results revealed that the Maxwell 16 from Promega (Mannheim, Germany) seems to be the superior system for DNA extraction from FFPE material. The extracts had a 1.3-24.6-fold higher DNA concentration in comparison to the other extraction systems, a higher quality and were most suitable for downstream applications. The comparison of the five quantification methods showed intermethod variations but all methods could be used to estimate the right amount for PCR amplification and for massively parallel sequencing. Interestingly, the best results in massively parallel sequencing were obtained with a DNA input of 15 ng determined by the NanoDrop 2000c spectrophotometer (Thermo Fisher Scientific, Waltham, MA, USA). No difference could be detected in mutation analysis based on the results of the quantification methods. These findings emphasise, that it is particularly important to choose the most reliable and constant DNA extraction system, especially when using small biopsies and low elution volumes, and that all common DNA quantification techniques can be used for downstream applications like massively parallel sequencing."],["dc.identifier.doi","10.1371/journal.pone.0104566"],["dc.identifier.isi","000343231900073"],["dc.identifier.pmid","25105902"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10632"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32676"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Comparison of Pre-Analytical FFPE Sample Preparation Methods and Their Impact on Massively Parallel Sequencing in Routine Diagnostics"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","291"],["dc.bibliographiccitation.journal","BMC Cancer"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Heydt, Carina"],["dc.contributor.author","Kumm, Niklas"],["dc.contributor.author","Fassunke, Jana"],["dc.contributor.author","Kuenstlinger, Helen"],["dc.contributor.author","Ihle, Michaela Angelika"],["dc.contributor.author","Scheel, Andreas"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Haller, Florian"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Odenthal, Margarete"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.date.accessioned","2018-11-07T09:58:30Z"],["dc.date.available","2018-11-07T09:58:30Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: Personalised medicine and targeted therapy have revolutionised cancer treatment. However, most patients develop drug resistance and relapse after showing an initial treatment response. Two theories have been postulated; either secondary resistance mutations develop de novo during therapy by mutagenesis or they are present in minor subclones prior to therapy. In this study, these two theories were evaluated in gastrointestinal stromal tumours (GISTs) where most patients develop secondary resistance mutations in the KIT gene during therapy with tyrosine kinase inhibitors. Methods: We used a cohort of 33 formalin-fixed, paraffin embedded (FFPE) primary GISTs and their corresponding recurrent tumours with known mutational status. The primary tumours were analysed for the secondary mutations of the recurrences, which had been identified previously. The primary tumours were resected prior to tyrosine kinase inhibitor therapy. Three ultrasensitive, massively parallel sequencing approaches on the GS Junior (Roche, Mannheim, Germany) and the MiSeq (TM) (Illumina, San Diego, CA, USA) were applied. Additionally, nine fresh-frozen samples resected prior to therapy were analysed for the most common secondary resistance mutations. Results: With a sensitivity level of down to 0.02%, no pre-existing resistant subclones with secondary KIT mutations were detected in primary GISTs. The sensitivity level varied for individual secondary mutations and was limited by sequencing artefacts on both systems. Artificial T > C substitutions at the position of the exon 13 p.V654A mutation, in particular, led to a lower sensitivity, independent from the source of the material. Fresh-frozen samples showed the same range of artificially mutated allele frequencies as the FFPE material. Conclusions: Although we achieved a sufficiently high level of sensitivity, neither in the primary FFPE nor in the fresh-frozen GISTs we were able to detect pre-existing resistant subclones of the corresponding known secondary resistance mutations of the recurrent tumours. This supports the theory that secondary KIT resistance mutations develop under treatment by \"de novo\" mutagenesis. Alternatively, the detection limit of two mutated clones in 10,000 wild-type clones might not have been high enough or heterogeneous tissue samples, per se, might not be suitable for the detection of very small subpopulations of mutated cells."],["dc.identifier.doi","10.1186/s12885-015-1311-0"],["dc.identifier.isi","000353019500001"],["dc.identifier.pmid","25886408"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12358"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37374"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2407"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Massively parallel sequencing fails to detect minor resistant subclones in tissue samples prior to tyrosine kinase inhibitor therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]