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KRAS signaling in m...
KRAS signaling in malignant pleural mesothelioma
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- Marazioti, Antonia (author)
- Ludwig-Maximilian University of Munich
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- Krontira, Anthi C (author)
- University of Patras
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- Behrend, Sabine J (author)
- Ludwig-Maximilian University of Munich
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- Giotopoulou, Georgia A (author)
- Ludwig-Maximilian University of Munich
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- Ntaliarda, Giannoula (author)
- University of Patras
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- Blanquart, Christophe (author)
- University of Nantes
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- Bayram, Hasan (author)
- Koc University
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- Iliopoulou, Marianthi (author)
- University of Patras
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- Vreka, Malamati (author)
- Ludwig-Maximilian University of Munich
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- Trassl, Lilith (author)
- Ludwig-Maximilian University of Munich
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Pepe, Mario A A (author)
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Hackl, Caroline M (author)
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Klotz, Laura V (author)
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Weiss, Stefanie A I (author)
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Koch, Ina (author)
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Lindner, Michael (author)
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Hatz, Rudolph A (author)
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Behr, Juergen (author)
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- Wagner, Darcy E (author)
- Lund University,Lunds universitet,Lungbioengineering och regeneration,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Lung Bioengineering and Regeneration,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Ludwig-Maximilian University of Munich,German Center for Lung Research (DZL)
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Papadaki, Helen (author)
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Antimisiaris, Sophia G (author)
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Jean, Didier (author)
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Deshayes, Sophie (author)
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Grégoire, Marc (author)
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Kayalar, Özgecan (author)
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Mortazavi, Deniz (author)
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Dilege, Şükrü (author)
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Tanju, Serhan (author)
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Erus, Suat (author)
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Yavuz, Ömer (author)
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Bulutay, Pınar (author)
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Fırat, Pınar (author)
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Psallidas, Ioannis (author)
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Spella, Magda (author)
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Giopanou, Ioanna (author)
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Lilis, Ioannis (author)
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Lamort, Anne-Sophie (author)
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Stathopoulos, Georgios T (author)
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(creator_code:org_t)
- 2021-12-13
- 2022
- English.
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In: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 14:2
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Abstract
Subject headings
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- Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Marazioti, Anton ...
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Krontira, Anthi ...
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Behrend, Sabine ...
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Giotopoulou, Geo ...
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Ntaliarda, Giann ...
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Blanquart, Chris ...
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show more...
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Bayram, Hasan
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Iliopoulou, Mari ...
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Vreka, Malamati
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Trassl, Lilith
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Pepe, Mario A A
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Hackl, Caroline ...
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Klotz, Laura V
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Weiss, Stefanie ...
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Koch, Ina
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Lindner, Michael
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Hatz, Rudolph A
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Behr, Juergen
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Wagner, Darcy E
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Papadaki, Helen
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Antimisiaris, So ...
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Jean, Didier
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Deshayes, Sophie
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Grégoire, Marc
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Kayalar, Özgecan
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Mortazavi, Deniz
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Dilege, Şükrü
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Tanju, Serhan
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Erus, Suat
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Yavuz, Ömer
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Bulutay, Pınar
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Fırat, Pınar
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Psallidas, Ioann ...
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Spella, Magda
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Giopanou, Ioanna
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Lilis, Ioannis
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Lamort, Anne-Sop ...
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Stathopoulos, Ge ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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EMBO Molecular M ...
- By the university
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Lund University