The integrated landscape of driver genomic alterations in glioblastoma
| العنوان: | The integrated landscape of driver genomic alterations in glioblastoma |
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| المؤلفون: | Pietro Zoppoli, Alan X. Ji, Darell D. Bigner, Jeffrey N. Bruce, Francesco Niola, Gilbert G. Privé, Gaurav Gupta, Carla Danussi, Francesco Abate, Anna Lasorella, Vladimir Trifonov, Kenneth Aldape, David J. Pisapia, Angelica Castano, Stephen T. Keir, Marie Lia, Igor Dolgalev, Adriana Heguy, Peter Canoll, Antonio Iavarone, Roger E. McLendon, Paola Porrati, Tom Mikkelsen, Joseph M. Chan, Serena Pellegatta, Raul Rabadan, Veronique Frattini, Gaetano Finocchiaro, Hai Yan |
| المساهمون: | Frattini, V., Trifonov, V., Chan, J. M., Castano, A., Lia, M., Abate, F., Keir, S. T., Ji, A. X., Zoppoli, P., Niola, F., Danussi, C., Dolgalev, I., Porrati, P., Pellegatta, S., Heguy, A., Gupta, G., Pisapia, D. J., Canoll, P., Bruce, J. N., Mclendon, R. E., Yan, H., Aldape, K., Finocchiaro, G., Mikkelsen, T., Prive, G. G., Bigner, D. D., Lasorella, A., Rabadan, R., Iavarone, A. |
| المصدر: | Nature genetics |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Delta Catenin, Somatic cell, Biology, medicine.disease_cause, Article, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Glioma, Genetics, medicine, Humans, Copy-number variation, Gene, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Mutation, Brain Neoplasms, Catenins, Genomics, medicine.disease, 3. Good health, ErbB Receptors, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Cancer research, Stem cell, Glioblastoma, Transcription Factors |
| الوصف: | Glioblastoma is one of the most challenging forms of cancer to treat. Here we describe a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma. We found mutations with loss of heterozygosity in LZTR1, encoding an adaptor of CUL3-containing E3 ligase complexes. Mutations and deletions disrupt LZTR1 function, which restrains the self renewal and growth of glioma spheres that retain stem cell features. Loss-of-function mutations in CTNND2 target a neural-specific gene and are associated with the transformation of glioma cells along the very aggressive mesenchymal phenotype. We also report recurrent translocations that fuse the coding sequence of EGFR to several partners, with EGFR-SEPT14 being the most frequent functional gene fusion in human glioblastoma. EGFR-SEPT14 fusions activate STAT3 signaling and confer mitogen independence and sensitivity to EGFR inhibition. These results provide insights into the pathogenesis of glioblastoma and highlight new targets for therapeutic intervention. © 2013 Nature America, Inc. All rights reserved. |
| تدمد: | 1546-1718 1061-4036 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a57c02f3b234b7311cad9e39f6a47109Test https://doi.org/10.1038/ng.2734Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a57c02f3b234b7311cad9e39f6a47109 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461718 10614036 |
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