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| Verfasst von: | Lodde, Georg Christian [VerfasserIn]  |
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| | Jansen, Philipp [VerfasserIn] |
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| | Herbst, Rudolf [VerfasserIn] |
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| | Terheyden, Patrick [VerfasserIn] |
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| | Utikal, Jochen [VerfasserIn] |
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| | Pföhler, Claudia [VerfasserIn] |
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| | Ulrich, Jens [VerfasserIn] |
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| | Kreuter, Alexander [VerfasserIn] |
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| | Mohr, Peter [VerfasserIn] |
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| | Gutzmer, Ralf [VerfasserIn] |
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| | Meier, Friedegund [VerfasserIn] |
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| | Dippel, Edgar [VerfasserIn] |
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| | Weichenthal, Michael [VerfasserIn] |
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| | Sucker, Antje [VerfasserIn] |
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| | Placke, Jan-Malte [VerfasserIn] |
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| | Zaremba, Anne [VerfasserIn] |
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| | Albrecht, Lea Jessica [VerfasserIn] |
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| | Kowall, Bernd [VerfasserIn] |
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| | Galetzka, Wolfgang [VerfasserIn] |
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| | Becker, Jürgen C. [VerfasserIn] |
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| | Tasdogan, Alpaslan [VerfasserIn] |
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| | Zimmer, Lisa [VerfasserIn] |
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| | Livingstone, Elisabeth [VerfasserIn] |
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| | Hadaschik, Eva [VerfasserIn] |
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| | Schadendorf, Dirk [VerfasserIn] |
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| | Ugurel, Selma [VerfasserIn] |
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| | Griewank, Klaus [VerfasserIn] |
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| Titel: | Characterisation and outcome of RAC1 mutated melanoma |
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| Verf.angabe: | Georg C. Lodde, Philipp Jansen, Rudolf Herbst, Patrick Terheyden, Jochen Utikal, Claudia Pföhler, Jens Ulrich, Alexander Kreuter, Peter Mohr, Ralf Gutzmer, Friedegund Meier, Edgar Dippel, Michael Weichenthal, Antje Sucker, Jan-Malte Placke, Anne Zaremba, Lea Jessica Albrecht, Bernd Kowall, Wolfgang Galetzka, Jürgen C. Becker, Alpaslan Tasdogan, Lisa Zimmer, Elisabeth Livingstone, Eva Hadaschik, Dirk Schadendorf, Selma Ugurel, Klaus Griewank |
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| E-Jahr: | 2023 |
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| Jahr: | April 2023 |
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| Umfang: | 10 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Online verfügbar: 18. Januar 2023, Artikelversion: 9. Februar 2023 ; Gesehen am 16.08.2023 |
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| Titel Quelle: | Enthalten in: European journal of cancer |
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| Ort Quelle: | Amsterdam [u.a.] : Elsevier, 1992 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | 183(2023) vom: Apr., Seite 1-10 |
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| ISSN Quelle: | 1879-0852 |
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| Abstract: | Background - Activating hot spot R29S mutations in RAC1, a small GTPase influencing several cellular processes including cell proliferation and cytoskeleton rearrangement, have been reported in up to 9% of sun-exposed melanomas. Clinical characteristics and treatment implications of RAC1 mutations in melanoma remain unclear. - Methods - We investigated the largest set (n = 64) of RAC1 mutated melanoma patients reported to date, including a retrospective single institution cohort (n = 34) from the University Hospital Essen and a prospective multicentre cohort (n = 30) from the translational study Tissue Registry in Melanoma (TRIM; CA209-578), for patient and tumour characteristics as well as therapy outcomes. - Results - From 3037 sequenced melanoma samples screened RAC1 mutations occurred in ∼2% of samples (64/3037). The most common RAC1 mutation was P29S (95%, 61/64). The majority of tumours had co-occuring MAP kinase mutations (88%, 56/64); mostly activating NRAS (47%, 30/64) mutations, followed by activating BRAF (28%, 18/64) and NF1 (25%, 16/64) mutations. RAC1 mutated melanomas were almost exclusively of cutaneous origin (84%, 54/64) or of unknown primary (MUP, 14%, 9/64). C > T alterations were the most frequent mutation type identified demonstrating a UV-signature for RAC1 mutated melanoma. Most patients with unresectable disease (39) received immune checkpoint inhibitors (ICI) (77%, 30/39). Objective response rate of first-line treatment in patients with stage III/IV disease was 21%; median overall survival was 47.8 months. - Conclusions - RAC1 mutated melanomas are rare, mostly of cutaneous origin and frequently harbour concomitant MAP kinase mutations, particularly in NRAS. Patients with advanced disease benefit from systemic treatment with ICI. |
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| DOI: | doi:10.1016/j.ejca.2023.01.009 |
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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: https://doi.org/10.1016/j.ejca.2023.01.009 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S0959804923000175 |
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| | DOI: https://doi.org/10.1016/j.ejca.2023.01.009 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Immune checkpoint inhibition |
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| | Melanoma |
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| | mutation |
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| | Mutational analysis |
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| | Systemic treatment |
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| | Targeted therapy |
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| K10plus-PPN: | 1856303721 |
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| Verknüpfungen: | → Zeitschrift |
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Characterisation and outcome of RAC1 mutated melanoma / Lodde, Georg Christian [VerfasserIn]; April 2023 (Online-Ressource)
