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| Verfasst von: | Polubothu, Satyamaanasa [VerfasserIn]  |
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| | Bender, Nicole [VerfasserIn] |
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| | Muthiah, Siobhan [VerfasserIn] |
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| | Zecchin, Davide [VerfasserIn] |
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| | Demetriou, Charalambos [VerfasserIn] |
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| | Martin, Sara Barberan [VerfasserIn] |
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| | Malhotra, Sony [VerfasserIn] |
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| | Travnickova, Jana [VerfasserIn] |
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| | Zeng, Zhiqiang [VerfasserIn] |
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| | Böhm, Markus [VerfasserIn] |
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| | Barbarot, Sebastien [VerfasserIn] |
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| | Cottrell, Catherine [VerfasserIn] |
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| | Davies, Olivia [VerfasserIn] |
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| | Baselga, Eulalia [VerfasserIn] |
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| | Burrows, Nigel P. [VerfasserIn] |
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| | Carmignac, Virginie [VerfasserIn] |
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| | Diaz, Joey Santiago [VerfasserIn] |
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| | Fink, Christine [VerfasserIn] |
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| | Hänßle, Holger [VerfasserIn] |
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| | Happle, Rudolf [VerfasserIn] |
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| | Harland, Mark [VerfasserIn] |
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| | Majerowski, Jacquelyn [VerfasserIn] |
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| | Vabres, Pierre [VerfasserIn] |
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| | Vincent, Marie [VerfasserIn] |
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| | Newton-Bishop, Julia A. [VerfasserIn] |
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| | Bishop, D. Tim [VerfasserIn] |
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| | Siegel, Dawn [VerfasserIn] |
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| | Patton, E. Elizabeth [VerfasserIn] |
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| | Topf, Maya [VerfasserIn] |
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| | Rajan, Neil [VerfasserIn] |
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| | Drolet, Beth [VerfasserIn] |
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| | Kinsler, Veronica A. [VerfasserIn] |
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| Titel: | PTPN11 mosaicism causes a spectrum of pigmentary and vascular neurocutaneous disorders and predisposes to melanoma |
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| Verf.angabe: | Satyamaanasa Polubothu, Nicole Bender, Siobhan Muthiah, Davide Zecchin, Charalambos Demetriou, Sara Barberan Martin, Sony Malhotra, Jana Travnickova, Zhiqiang Zeng, Markus Böhm, Sebastien Barbarot, Catherine Cottrell, Olivia Davies, Eulalia Baselga, Nigel P. Burrows, Virginie Carmignac, Joey Santiago Diaz, Christine Fink, Holger A. Haenssle, Rudolf Happle, Mark Harland, Jacquelyn Majerowski, Pierre Vabres, Marie Vincent, Julia A. Newton-Bishop, D. Tim Bishop, Dawn Siegel, E. Elizabeth Patton, Maya Topf, Neil Rajan, Beth Drolet and Veronica A. Kinsler |
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| E-Jahr: | 2023 |
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| Jahr: | June 2023 |
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| Umfang: | 13 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Online verfügbar: 23. Dezember 2022, Artikelversion: 19. Mai 2023 ; Gesehen am 28.07.2023 |
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| Titel Quelle: | Enthalten in: The journal of investigative dermatology |
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| Ort Quelle: | Amsterdam : Elsevier, 1938 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | 143(2023), 6 vom: Juni, Seite 1042-1051.e3 |
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| ISSN Quelle: | 1523-1747 |
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| Abstract: | Phakomatosis pigmentovascularis is a diagnosis that denotes the coexistence of pigmentary and vascular birthmarks of specific types, accompanied by variable multisystem involvement, including CNS disease, asymmetrical growth, and a predisposition to malignancy. Using a tight phenotypic group and high-depth next-generation sequencing of affected tissues, we discover here clonal mosaic variants in gene PTPN11 encoding SHP2 phosphatase as a cause of phakomatosis pigmentovascularis type III or spilorosea. Within an individual, the same variant is found in distinct pigmentary and vascular birthmarks and is undetectable in blood. We go on to show that the same variants can cause either the pigmentary or vascular phenotypes alone, and drive melanoma development within pigmentary lesions. Protein structure modeling highlights that although variants lead to loss of function at the level of the phosphatase domain, resultant conformational changes promote longer ligand binding. In vitro modeling of the missense variants confirms downstream MAPK pathway overactivation and widespread disruption of human endothelial cell angiogenesis. Importantly, patients with PTPN11 mosaicism theoretically risk passing on the variant to their children as the germline RASopathy Noonan syndrome with lentigines. These findings improve our understanding of the pathogenesis and biology of nevus spilus and capillary malformation syndromes, paving the way for better clinical management. |
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| DOI: | doi:10.1016/j.jid.2022.09.661 |
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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.
kostenfrei: Volltext: https://doi.org/10.1016/j.jid.2022.09.661 |
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| | kostenfrei: Volltext: https://www.sciencedirect.com/science/article/pii/S0022202X22028913 |
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| | DOI: https://doi.org/10.1016/j.jid.2022.09.661 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1853859702 |
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| Verknüpfungen: | → Zeitschrift |
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PTPN11 mosaicism causes a spectrum of pigmentary and vascular neurocutaneous disorders and predisposes to melanoma / Polubothu, Satyamaanasa [VerfasserIn]; June 2023 (Online-Ressource)
