Schildhaus, Hans-Ulrich

[["dc.bibliographiccitation.journal","Oncology Research and Treatment"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Scheffler, M."],["dc.contributor.author","Schultheis, A."],["dc.contributor.author","Michels, Sebastian"],["dc.contributor.author","Teixido, Cristina"],["dc.contributor.author","Hartmann, Wolfgang"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Sebastian, Martin"],["dc.contributor.author","Serke, Monika Heidi"],["dc.contributor.author","Kropf-Sanchen, Cornelia"],["dc.contributor.author","Wittersheim, M."],["dc.contributor.author","Puetz, K."],["dc.contributor.author","Binot, Elke"],["dc.contributor.author","Schildhaus, H.-U."],["dc.contributor.author","Heukamp, Lukas Carl"],["dc.contributor.author","Rosell, Rafael"],["dc.contributor.author","Buettner, Reinhardt"],["dc.contributor.author","Wolf, J."],["dc.date.accessioned","2018-11-07T09:34:02Z"],["dc.date.available","2018-11-07T09:34:02Z"],["dc.date.issued","2014"],["dc.format.extent","66"],["dc.identifier.isi","000343816900151"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32093"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","2296-5262"],["dc.relation.issn","2296-5270"],["dc.title","ROS1 rearrangement in non-small cell lung cancer (NSCLC): Prognostic and predicitve impact and genetic variability"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","206"],["dc.bibliographiccitation.journal","Human Pathology"],["dc.bibliographiccitation.lastpage","214"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Huss, Sebastian"],["dc.contributor.author","Pasternack, Helen"],["dc.contributor.author","Ihle, Michaela Angelika"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Heitkoetter, Birthe"],["dc.contributor.author","Hartmann, Wolfgang"],["dc.contributor.author","Trautmann, Marcel"],["dc.contributor.author","Gevensleben, Heidrun"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Wardelmann, Eva"],["dc.date.accessioned","2018-11-07T10:25:18Z"],["dc.date.available","2018-11-07T10:25:18Z"],["dc.date.issued","2017"],["dc.description.abstract","In KIT/PDGFRA wild-type gastrointestinal stromal tumors (wt-GISTs), BRAF mutations are regarded as alternative pathogenic events driving tumorigenesis. In our study, we aimed at analyzing a large cohort (n = 444) of GISTs for BRAF mutations using molecular and immunohistochemical methods. More than 3000 GIST samples from caucasian patients were available in our GIST and Sarcoma Registry NRW. Of these, we selected 172 wt-GISTs to evaluate the frequency of BRAF mutations. Furthermore, 272 GISTs with a representative KIT and PDGFRA mutational status were selected. BRAF mutational status was evaluated by high-resolution melting analysis, Sanger sequencing, and VE1 immunohistochemistry. A BRAF mutation (p.V600E) was found in 7 cases (3.9%) of the wt-GIST cohort. In 2 cases, multiple synchronous tumors harbored the same somatic BRAF mutation. VE1 immunohistochemical staining had a sensitivity of 81.8% and a specificity of 97.5% to detect BRAF p.V600E mutations. Analyzing our cases and the cases reported in the literature (n = 37), the percentage of intermediate and high-risk BRAF-mutated wt-GISTs (17/31; 54.8%) was comparable to that recorded for large GIST cohorts irrespective of the mutational status. BRAF mutations are rare events in wt-GISTs, and VE1 immunohistochemistry appears to be a valuable pre-screening tool for the detection of BRAF p.V600E mutations. BRAF mutations in GISTs do not seem to have a prognostic value per se. However, as BRAF inhibition represents a therapeutic option to control disease, we suggest the assessment of the BRAF mutational status, especially in the setting of advanced GIST disease. (C) 2017 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.humpath.2017.01.005"],["dc.identifier.isi","000400230800027"],["dc.identifier.pmid","28159677"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42831"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","1532-8392"],["dc.relation.issn","0046-8177"],["dc.title","Clinicopathological and molecular features of a large cohort of gastrointestinal stromal tumors (GISTs) and review of the literature: BRAF mutations in KIT/PDGFRA wild-type GISTs are rare events"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1468"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Modern Pathology"],["dc.bibliographiccitation.lastpage","1477"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Deml, Karl-Friedrich"],["dc.contributor.author","Schmitz, Katja"],["dc.contributor.author","Meiboom, Maren"],["dc.contributor.author","Binot, Elke"],["dc.contributor.author","Hauke, Sven"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Buettner, Reinhard"],["dc.date.accessioned","2018-11-07T09:18:10Z"],["dc.date.available","2018-11-07T09:18:10Z"],["dc.date.issued","2013"],["dc.description.abstract","Reliable detection of anaplastic lymphoma kinase (ALK) rearrangements is a prerequisite for personalized treatment of lung cancer patients, as ALK rearrangements represent a predictive biomarker for the therapy with specific tyrosine kinase inhibitors. Currently, fluorescent in situ hybridization (FISH) is considered to be the standard method for assessing formalin-fixed and paraffin-embedded tissue for ALK inversions and translocations. However, FISH requires a specialized equipment, the signals fade rapidly and it is difficult to detect overall morphology and tumor heterogeneity. Chromogenic in situ hybridization (CISH) has been successfully introduced as an alternative test for the detection of several genetic aberrations. This study validates a newly developed ALK CISH assay by comparing FISH and CISH signal patterns in lung cancer samples with and without ALK rearrangements. One hundred adenocarcinomas of the lung were included in this study, among them 17 with known ALK rearrangement. FISH and CISH were carried out and evaluated according to the manufacturers' recommendations. For both assays, tumors were considered positive if >= 15% of tumor cells showed either isolated 3' signals or break-apart patterns or a combination of both. A subset of tumors was exemplarily examined by using a novel EML4 (echinoderm microtubule-associated protein-like 4) CISH probe. Red, green and fusion CISH signals were clearcut and different signal patterns were easily recognized. The percentage of aberrant tumor cells was statistically highly correlated (P<0.001) between FISH and CISH. On the basis of 86 samples that were evaluable by ALK CISH, we found a 100% sensitivity and 100% specificity of this assay. Furthermore, EML4 rearrangements could be recognized by CISH. CISH is a highly reliable, sensitive and specific method for the detection of ALK gene rearrangements in pulmonary adenocarcinomas. Our results suggest that CISH might serve as a suitable alternative to FISH, which is the current gold standard."],["dc.description.sponsorship","Lung Cancer Group Cologne (LCGC)"],["dc.identifier.doi","10.1038/modpathol.2013.95"],["dc.identifier.isi","000326686700007"],["dc.identifier.pmid","23743932"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28344"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1530-0285"],["dc.relation.issn","0893-3952"],["dc.title","Chromogenic in situ hybridization is a reliable assay for detection of ALK rearrangements in adenocarcinomas 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.issue","9"],["dc.bibliographiccitation.journal","Journal of Thoracic Oncology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Scheel, Andreas Hans"],["dc.contributor.author","Schmitz, Katja"],["dc.contributor.author","Wilsberg, Lea"],["dc.contributor.author","Fischer, Rieke N."],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Binot, Elke"],["dc.contributor.author","Plenker, Dennis"],["dc.contributor.author","Wolf, Juergen"],["dc.contributor.author","Tsuta, Koji"],["dc.contributor.author","Kohno, Takashi"],["dc.contributor.author","Thomas, Roman K."],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Buettner, Reinhard"],["dc.date.accessioned","2018-11-07T09:51:52Z"],["dc.date.available","2018-11-07T09:51:52Z"],["dc.date.issued","2015"],["dc.format.extent","S702"],["dc.identifier.isi","000370365103353"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35997"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.publisher.place","New york"],["dc.relation.issn","1556-1380"],["dc.relation.issn","1556-0864"],["dc.title","Prevalence of NRG1 fusions in Caucasian NSCLC patients determined by fluorescence in situ hybridisation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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.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.firstpage","573"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Human Pathology"],["dc.bibliographiccitation.lastpage","582"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Kuenstlinger, Helen"],["dc.contributor.author","Binot, Elke"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Huss, Sebastian"],["dc.contributor.author","Wardelmann, Eva"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.date.accessioned","2018-11-07T09:43:24Z"],["dc.date.available","2018-11-07T09:43:24Z"],["dc.date.issued","2014"],["dc.description.abstract","The mutational status of KIT and PDGFRA is highly relevant for prognosis and therapy prediction in gastrointestinal stromal tumors (GIST). PDGFRA exon 18 mutations have direct therapeutic implications since it is crucial to distinguish mutations associated with sensitivity to tyrosine kinase inhibitors from those causing primary resistance, eg, the most common exon 18 mutation p.D842V. In response to a growing demand for reliable, faster and more sensitive methods we established and validated a high-resolution melting (BRM) assay for PDGFRA exon 18. A total of 159 GIST samples were comparatively analyzed by FIRM and direct Sanger sequencing. We demonstrate that BRM provides highly reliable mutational results with higher sensitivity and shorter time to diagnosis compared to Sanger sequencing. We determined the sensitivity threshold of FIRM at 6% of mutated alleles. PDGFRA exon 18 wild-type status and the most common p.D842V resistance mutation (together representing >90% of the cases) can be detected specifically by FIRM. Other rare mutations can be pre-screened by FIRM and afterwards determined precisely by DNA sequencing. In this way we detected four novel mutations in PDGFRA exon 18, two of which were associated with an aggressive clinical course. Including these new mutations, we provide a comprehensive overview of all 60 currently known subtypes of PDGFRA exon 18 mutations in GIST. Seven of them (accounting for about 75% of all exon 18-mutated GISTs) are reported to be resistant to imatinib. However, there are at least 10 other mutations which are regarded as sensitive to tyrosine kinase inhibitors. (C) 2014 Elsevier Inc. All rights reserved."],["dc.description.sponsorship","Novartis Oncology"],["dc.identifier.doi","10.1016/j.humpath.2013.10.025"],["dc.identifier.isi","000331854400017"],["dc.identifier.pmid","24444465"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34178"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","1532-8392"],["dc.relation.issn","0046-8177"],["dc.title","High-resolution melting analysis is a sensitive diagnostic tool to detect imatinib-resistant and imatinib-sensitive PDGFRA exon 18 mutations in gastrointestinal stromal tumors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]