| |  Online-Ressource |
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| Verfasst von: | Kovac, Michal [VerfasserIn]  |
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| | Woolley, Connor [VerfasserIn] |
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| | Ribi, Sebastian [VerfasserIn] |
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| | Blattmann, Claudia [VerfasserIn] |
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| | Roth, Eva Kathrin [VerfasserIn] |
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| | Morini, Marco [VerfasserIn] |
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| | Kovacova, Monika [VerfasserIn] |
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| | Ameline, Baptiste [VerfasserIn] |
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| | Kulozik, Andreas [VerfasserIn] |
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| | Bielack, Stefan [VerfasserIn] |
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| | Hartmann, Wolfgang [VerfasserIn] |
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| | Ballinger, Mandy L. [VerfasserIn] |
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| | Thomas, David M. [VerfasserIn] |
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| | Tomlinson, Ian [VerfasserIn] |
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| | Nathrath, Michaela [VerfasserIn] |
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| | Heinimann, Karl [VerfasserIn] |
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| | Baumhoer, Daniel [VerfasserIn] |
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| Titel: | Germline RET variants underlie a subset of paediatric osteosarcoma |
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| Verf.angabe: | Michal Kovac, Connor Woolley, Sebastian Ribi, Claudia Blattmann, Eva Roth, Marco Morini, Monika Kovacova, Baptiste Ameline, Andreas Kulozik, Stefan Bielack, Wolfgang Hartmann, Mandy L. Ballinger, David M. Thomas, Ian Tomlinson, Michaela Nathrath, Karl Heinimann, Daniel Baumhoer |
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| Jahr: | 2021 |
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| Jahr des Originals: | 2020 |
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| Umfang: | 5 S. |
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| Teil: | volume:58 |
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| | year:2021 |
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| | number:1 |
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| | pages:20-24 |
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| | extent:5 |
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| Fussnoten: | Published Online First 16 March 2020 ; Gesehen am 09.03.2021 |
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| Titel Quelle: | Enthalten in: Journal of medical genetics |
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| Ort Quelle: | London : BMJ Publishing Group, 1964 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 58(2021), 1, Seite 20-24 |
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| ISSN Quelle: | 1468-6244 |
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| Abstract: | Background Although considerable effort has been put into decoding of the osteosarcoma genome, very little is known about germline mutations that underlie this primary malignant tumour of bone. - Methods and results We followed here a coincidental finding in a multiple endocrine neoplasia family in which a 32-year-old patient carrying a germline pathogenic RET mutation developed an osteosarcoma 2 years after the resection of a medullary thyroid carcinoma. Sequencing analysis of additional 336 patients with osteosarcoma led to the identification of germline activating mutations in the RET proto-oncogene in three cases and somatic amplifications of the gene locus in five matched tumours (4%, n=5/124 tumours). Functional analysis of the pathogenic variants together with an integrative analysis of osteosarcoma genomes confirmed that the mutant RET proteins couple functional kinase activity to dysfunctional ligand binding. RET mutations further co-operated with alterations in TP53 and RB1, suggesting that osteosarcoma pathogenesis bears reminiscence to the stepwise model of medullary thyroid carcinoma. - Conclusions After Li-Fraumeni-predisposing mutations in TP53, RET becomes the second most mutated cancer-predisposing gene in the germline of patients with osteosarcoma. Hence, early identification of RET mutation carriers can help to identify at-risk family members and carry out preventive measures. |
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| DOI: | doi:10.1136/jmedgenet-2019-106734 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1136/jmedgenet-2019-106734 |
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| | Volltext: https://jmg.bmj.com/content/58/1/20 |
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| | DOI: https://doi.org/10.1136/jmedgenet-2019-106734 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | calcium and bone |
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| | molecular genetics |
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| | paediatric oncology |
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| K10plus-PPN: | 1750865297 |
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| Verknüpfungen: | → Zeitschrift |
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Germline RET variants underlie a subset of paediatric osteosarcoma / Kovac, Michal [VerfasserIn]; 2021 (Online-Ressource)
