[{"doi":"10.1245/s10434-022-12681-z","keyword":["Oncology","Surgery"],"language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"other","id":"12205","status":"public"}]},"acknowledgement":"This work was supported by European Commission’s Seventh Framework Programme under Grant Agreement No. 279113 (OCTIPS; www.octips.eu).","author":[{"last_name":"Glajzer","first_name":"Jacek","full_name":"Glajzer, Jacek"},{"last_name":"Castillo-Tong","full_name":"Castillo-Tong, Dan Cacsire","first_name":"Dan Cacsire"},{"first_name":"Rolf","full_name":"Richter, Rolf","last_name":"Richter"},{"last_name":"Vergote","first_name":"Ignace","full_name":"Vergote, Ignace"},{"full_name":"Kulbe, Hagen","first_name":"Hagen","last_name":"Kulbe"},{"last_name":"Vanderstichele","full_name":"Vanderstichele, Adriaan","first_name":"Adriaan"},{"last_name":"Ruscito","full_name":"Ruscito, Ilary","first_name":"Ilary"},{"first_name":"Fabian","full_name":"Trillsch, Fabian","last_name":"Trillsch"},{"last_name":"Mustea","full_name":"Mustea, Alexander","first_name":"Alexander"},{"last_name":"Kreuzinger","first_name":"Caroline","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Gourley","first_name":"Charlie","full_name":"Gourley, Charlie"},{"first_name":"Hani","full_name":"Gabra, Hani","last_name":"Gabra"},{"last_name":"Taube","full_name":"Taube, Eliane T.","first_name":"Eliane T."},{"full_name":"Dorigo, Oliver","first_name":"Oliver","last_name":"Dorigo"},{"first_name":"David","full_name":"Horst, David","last_name":"Horst"},{"full_name":"Keunecke, Carlotta","first_name":"Carlotta","last_name":"Keunecke"},{"first_name":"Joanna","full_name":"Baum, Joanna","last_name":"Baum"},{"last_name":"Angelotti","first_name":"Timothy","full_name":"Angelotti, Timothy"},{"first_name":"Jalid","full_name":"Sehouli, Jalid","last_name":"Sehouli"},{"last_name":"Braicu","first_name":"Elena Ioana","full_name":"Braicu, Elena Ioana"}],"type":"journal_article","day":"01","title":"ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium","citation":{"mla":"Glajzer, Jacek, et al. “ASO Visual Abstract: Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome, and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer (HGSOC). A Multicenter, Retrospective Study of the Ovarian Cancer Therapy—Innovative Models Prolong Survival (OCTIPS) Consortium.” <i>Annals of Surgical Oncology</i>, vol. 30, Springer Nature, 2023, pp. 46–47, doi:<a href=\"https://doi.org/10.1245/s10434-022-12681-z\">10.1245/s10434-022-12681-z</a>.","ieee":"J. Glajzer <i>et al.</i>, “ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium,” <i>Annals of Surgical Oncology</i>, vol. 30. Springer Nature, pp. 46–47, 2023.","ista":"Glajzer J, Castillo-Tong DC, Richter R, Vergote I, Kulbe H, Vanderstichele A, Ruscito I, Trillsch F, Mustea A, Kreuzinger C, Gourley C, Gabra H, Taube ET, Dorigo O, Horst D, Keunecke C, Baum J, Angelotti T, Sehouli J, Braicu EI. 2023. ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium. Annals of Surgical Oncology. 30, 46–47.","chicago":"Glajzer, Jacek, Dan Cacsire Castillo-Tong, Rolf Richter, Ignace Vergote, Hagen Kulbe, Adriaan Vanderstichele, Ilary Ruscito, et al. “ASO Visual Abstract: Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome, and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer (HGSOC). A Multicenter, Retrospective Study of the Ovarian Cancer Therapy—Innovative Models Prolong Survival (OCTIPS) Consortium.” <i>Annals of Surgical Oncology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1245/s10434-022-12681-z\">https://doi.org/10.1245/s10434-022-12681-z</a>.","apa":"Glajzer, J., Castillo-Tong, D. C., Richter, R., Vergote, I., Kulbe, H., Vanderstichele, A., … Braicu, E. I. (2023). ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium. <i>Annals of Surgical Oncology</i>. Springer Nature. <a href=\"https://doi.org/10.1245/s10434-022-12681-z\">https://doi.org/10.1245/s10434-022-12681-z</a>","ama":"Glajzer J, Castillo-Tong DC, Richter R, et al. ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium. <i>Annals of Surgical Oncology</i>. 2023;30:46-47. doi:<a href=\"https://doi.org/10.1245/s10434-022-12681-z\">10.1245/s10434-022-12681-z</a>","short":"J. Glajzer, D.C. Castillo-Tong, R. Richter, I. Vergote, H. Kulbe, A. Vanderstichele, I. Ruscito, F. Trillsch, A. Mustea, C. Kreuzinger, C. Gourley, H. Gabra, E.T. Taube, O. Dorigo, D. Horst, C. Keunecke, J. Baum, T. Angelotti, J. Sehouli, E.I. Braicu, Annals of Surgical Oncology 30 (2023) 46–47."},"intvolume":"        30","status":"public","publication":"Annals of Surgical Oncology","department":[{"_id":"JoDa"}],"quality_controlled":"1","isi":1,"publisher":"Springer Nature","date_created":"2023-01-12T11:56:22Z","month":"01","page":"46-47","publication_identifier":{"eissn":["1534-4681"],"issn":["1068-9265"]},"scopus_import":"1","external_id":{"isi":["000879151800001"]},"date_updated":"2023-09-05T15:18:36Z","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","year":"2023","oa_version":"Published Version","article_type":"original","volume":30,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1245/s10434-022-12681-z"}],"oa":1,"publication_status":"published","_id":"12115","date_published":"2023-01-01T00:00:00Z","article_processing_charge":"No"},{"publication_identifier":{"issn":["1068-9265"],"eissn":["1534-4681"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_updated":"2023-09-05T15:18:37Z","scopus_import":"1","external_id":{"isi":["000852125500006"]},"year":"2023","oa_version":"Published Version","has_accepted_license":"1","article_type":"original","oa":1,"publication_status":"published","volume":30,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"file_date_updated":"2023-02-02T13:01:20Z","article_processing_charge":"No","_id":"12205","date_published":"2023-01-01T00:00:00Z","abstract":[{"lang":"eng","text":"Background: This study seeks to evaluate the impact of breast cancer (BRCA) gene status on tumor dissemination pattern, surgical outcome and survival in a multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian cancer (rOC).\r\n\r\nPatients and Methods: Medical records and follow-up data from 190 patients were gathered retrospectively. All patients had surgery at pOC and at least one further rOC surgery at four European high-volume centers. Patients were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut) and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor presentation, surgical outcome and survival data were analyzed between the two groups.\r\n\r\nResults: Patients with BRCAmut disease were on average 4 years younger and had significantly more tumor involvement upon diagnosis. Patients with BRCAmut disease showed higher debulking rates at all stages. Multivariate analysis showed that only patient age had significant predictive value for complete tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated with optimal debulking. Patients with BRCAmut disease showed significantly prolonged overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged in the BRCAmut group at all stages as well, reaching statistical significance during recurrence.\r\n\r\nConclusions: Patients with BRCAmut disease showed a more aggressive course of disease with earlier onset and more extensive tumor dissemination at pOC. However, surgical outcome and OS were significantly better in patients with BRCAmut disease compared with patients with BRCAwt disease. We therefore propose to consider BRCAmut status in regard to patient selection for cytoreductive surgery, especially in rOC."}],"file":[{"success":1,"date_created":"2023-02-02T13:01:20Z","content_type":"application/pdf","relation":"main_file","file_id":"12490","date_updated":"2023-02-02T13:01:20Z","access_level":"open_access","checksum":"36a1200e1011f4b2155a8041d0308f34","file_name":"2023_AnnalsSurgicalOncology_Glajzer.pdf","creator":"dernst","file_size":365865}],"acknowledgement":"E.I.B. is a Feodor Lynen fellow of the Humboldt Foundation and a participant of the Charité Clinical Scientist Program funded by the Charité Universitätsmedizin Berlin and the Berlin Institute of Health. This work was supported by European Commission’s Seventh Framework Programme under grant agreement no. 279113 (OCTIPS; www.octips.eu).\r\nOpen Access funding enabled and organized by Projekt DEAL.","related_material":{"record":[{"status":"public","relation":"other","id":"12115"}]},"ddc":["610"],"doi":"10.1245/s10434-022-12459-3","language":[{"iso":"eng"}],"keyword":["Oncology","Surgery"],"title":"Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium","citation":{"apa":"Glajzer, J., Castillo-Tong, D. C., Richter, R., Vergote, I., Kulbe, H., Vanderstichele, A., … Braicu, E. I. (2023). Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium. <i>Annals of Surgical Oncology</i>. Springer Nature. <a href=\"https://doi.org/10.1245/s10434-022-12459-3\">https://doi.org/10.1245/s10434-022-12459-3</a>","ama":"Glajzer J, Castillo-Tong DC, Richter R, et al. Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium. <i>Annals of Surgical Oncology</i>. 2023;30:35-45. doi:<a href=\"https://doi.org/10.1245/s10434-022-12459-3\">10.1245/s10434-022-12459-3</a>","short":"J. Glajzer, D.C. Castillo-Tong, R. Richter, I. Vergote, H. Kulbe, A. Vanderstichele, I. Ruscito, F. Trillsch, A. Mustea, C. Kreuzinger, C. Gourley, H. Gabra, E.T. Taube, O. Dorigo, D. Horst, C. Keunecke, J. Baum, T. Angelotti, J. Sehouli, E.I. Braicu, Annals of Surgical Oncology 30 (2023) 35–45.","mla":"Glajzer, Jacek, et al. “Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.” <i>Annals of Surgical Oncology</i>, vol. 30, Springer Nature, 2023, pp. 35–45, doi:<a href=\"https://doi.org/10.1245/s10434-022-12459-3\">10.1245/s10434-022-12459-3</a>.","ista":"Glajzer J, Castillo-Tong DC, Richter R, Vergote I, Kulbe H, Vanderstichele A, Ruscito I, Trillsch F, Mustea A, Kreuzinger C, Gourley C, Gabra H, Taube ET, Dorigo O, Horst D, Keunecke C, Baum J, Angelotti T, Sehouli J, Braicu EI. 2023. Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium. Annals of Surgical Oncology. 30, 35–45.","ieee":"J. Glajzer <i>et al.</i>, “Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium,” <i>Annals of Surgical Oncology</i>, vol. 30. Springer Nature, pp. 35–45, 2023.","chicago":"Glajzer, Jacek, Dan Cacsire Castillo-Tong, Rolf Richter, Ignace Vergote, Hagen Kulbe, Adriaan Vanderstichele, Ilary Ruscito, et al. “Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.” <i>Annals of Surgical Oncology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1245/s10434-022-12459-3\">https://doi.org/10.1245/s10434-022-12459-3</a>."},"type":"journal_article","author":[{"first_name":"Jacek","full_name":"Glajzer, Jacek","last_name":"Glajzer"},{"first_name":"Dan Cacsire","full_name":"Castillo-Tong, Dan Cacsire","last_name":"Castillo-Tong"},{"last_name":"Richter","first_name":"Rolf","full_name":"Richter, Rolf"},{"full_name":"Vergote, Ignace","first_name":"Ignace","last_name":"Vergote"},{"last_name":"Kulbe","first_name":"Hagen","full_name":"Kulbe, Hagen"},{"full_name":"Vanderstichele, Adriaan","first_name":"Adriaan","last_name":"Vanderstichele"},{"first_name":"Ilary","full_name":"Ruscito, Ilary","last_name":"Ruscito"},{"first_name":"Fabian","full_name":"Trillsch, Fabian","last_name":"Trillsch"},{"last_name":"Mustea","first_name":"Alexander","full_name":"Mustea, Alexander"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","first_name":"Caroline"},{"last_name":"Gourley","first_name":"Charlie","full_name":"Gourley, Charlie"},{"first_name":"Hani","full_name":"Gabra, Hani","last_name":"Gabra"},{"first_name":"Eliane T.","full_name":"Taube, Eliane T.","last_name":"Taube"},{"first_name":"Oliver","full_name":"Dorigo, Oliver","last_name":"Dorigo"},{"first_name":"David","full_name":"Horst, David","last_name":"Horst"},{"first_name":"Carlotta","full_name":"Keunecke, Carlotta","last_name":"Keunecke"},{"full_name":"Baum, Joanna","first_name":"Joanna","last_name":"Baum"},{"full_name":"Angelotti, Timothy","first_name":"Timothy","last_name":"Angelotti"},{"last_name":"Sehouli","full_name":"Sehouli, Jalid","first_name":"Jalid"},{"first_name":"Elena Ioana","full_name":"Braicu, Elena Ioana","last_name":"Braicu"}],"day":"01","isi":1,"publisher":"Springer Nature","status":"public","intvolume":"        30","department":[{"_id":"JoDa"}],"quality_controlled":"1","publication":"Annals of Surgical Oncology","page":"35-45","date_created":"2023-01-16T09:44:36Z","month":"01"},{"related_material":{"record":[{"status":"public","relation":"earlier_version","id":"7800"},{"status":"public","id":"12401","relation":"dissertation_contains"}],"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}]},"project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"},{"call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","grant_number":"W1232-B24"},{"grant_number":"F07807","name":"Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"}],"acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","ddc":["572"],"doi":"10.1038/s41467-021-23123-x","keyword":["General Biochemistry","Genetics and Molecular Biology"],"language":[{"iso":"eng"}],"title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","citation":{"apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058.","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>Nature Communications</i>, vol. 12, no. 1. Springer Nature, 2021.","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>."},"ec_funded":1,"type":"journal_article","author":[{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","first_name":"Jasmin","full_name":"Morandell, Jasmin"},{"last_name":"Schwarz","first_name":"Lena A","full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Basilico","full_name":"Basilico, Bernadette","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173"},{"last_name":"Tasciyan","full_name":"Tasciyan, Saren","first_name":"Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-8370-6161","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","last_name":"Dimchev","first_name":"Georgi A","full_name":"Dimchev, Georgi A"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","first_name":"Armel","last_name":"Nicolas"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline","full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger"},{"orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter","first_name":"Christoph","full_name":"Dotter, Christoph"},{"full_name":"Knaus, Lisa","first_name":"Lisa","last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"id":"D23090A2-9057-11EA-883A-A8396FC7A38F","last_name":"Dobler","full_name":"Dobler, Zoe","first_name":"Zoe"},{"first_name":"Emanuele","full_name":"Cacci, Emanuele","last_name":"Cacci"},{"full_name":"Schur, Florian KM","first_name":"Florian KM","last_name":"Schur","orcid":"0000-0003-4790-8078","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","full_name":"Danzl, Johann G","last_name":"Danzl"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","full_name":"Novarino, Gaia","first_name":"Gaia"}],"day":"24","isi":1,"publisher":"Springer Nature","status":"public","intvolume":"        12","publication":"Nature Communications","quality_controlled":"1","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"date_created":"2021-05-28T11:49:46Z","month":"05","publication_identifier":{"eissn":["2041-1723"]},"acknowledged_ssus":[{"_id":"PreCl"}],"external_id":{"isi":["000658769900010"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_updated":"2024-09-10T12:04:26Z","year":"2021","oa_version":"Published Version","has_accepted_license":"1","article_type":"original","oa":1,"publication_status":"published","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"volume":12,"file_date_updated":"2021-05-28T12:39:43Z","article_processing_charge":"No","issue":"1","date_published":"2021-05-24T00:00:00Z","_id":"9429","abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs."}],"file":[{"success":1,"date_created":"2021-05-28T12:39:43Z","relation":"main_file","file_id":"9430","content_type":"application/pdf","access_level":"open_access","date_updated":"2021-05-28T12:39:43Z","checksum":"337e0f7959c35ec959984cacdcb472ba","file_size":9358599,"creator":"kschuh","file_name":"2021_NatureCommunications_Morandell.pdf"}],"article_number":"3058"},{"acknowledged_ssus":[{"_id":"PreCl"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2024-09-10T12:04:26Z","has_accepted_license":"1","year":"2020","oa_version":"Preprint","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"file_date_updated":"2020-07-14T12:48:03Z","oa":1,"publication_status":"submitted","_id":"7800","date_published":"2020-01-11T00:00:00Z","abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages."}],"file":[{"checksum":"c6799ab5daba80efe8e2ed63c15f8c81","date_updated":"2020-07-14T12:48:03Z","access_level":"open_access","file_name":"2020.01.10.902064v1.full.pdf","creator":"rsix","file_size":2931370,"date_created":"2020-05-05T14:31:19Z","content_type":"application/pdf","file_id":"7801","relation":"main_file"}],"article_processing_charge":"No","doi":"10.1101/2020.01.10.902064 ","ddc":["570"],"language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"dissertation_contains","id":"8620","status":"public"},{"status":"public","relation":"later_version","id":"9429"}]},"project":[{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"type":"preprint","author":[{"last_name":"Morandell","first_name":"Jasmin","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Lena A","full_name":"Schwarz, Lena A"},{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","last_name":"Basilico","first_name":"Bernadette","full_name":"Basilico, Bernadette"},{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","first_name":"Saren","full_name":"Tasciyan, Saren","last_name":"Tasciyan"},{"full_name":"Nicolas, Armel","first_name":"Armel","last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","last_name":"Kreuzinger","first_name":"Caroline","full_name":"Kreuzinger, Caroline"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus","full_name":"Knaus, Lisa","first_name":"Lisa"},{"id":"D23090A2-9057-11EA-883A-A8396FC7A38F","last_name":"Dobler","first_name":"Zoe","full_name":"Dobler, Zoe"},{"first_name":"Emanuele","full_name":"Cacci, Emanuele","last_name":"Cacci"},{"full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"},{"first_name":"Gaia","full_name":"Novarino, Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"}],"day":"11","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","citation":{"short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>.","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>."},"status":"public","publication":"bioRxiv","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"publisher":"Cold Spring Harbor Laboratory","date_created":"2020-05-05T14:31:33Z","month":"01"}]