Characterisation and outcome of RAC1 mutated melanoma
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 i...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
April 2023
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| In: |
European journal of cancer
Year: 2023, Jahrgang: 183, Pages: 1-10 |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2023.01.009 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ejca.2023.01.009 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0959804923000175 
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| Verfasserangaben: | 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 |
MARC
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| 245 | 1 | 0 | |a Characterisation and outcome of RAC1 mutated melanoma |c 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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| 520 | |a 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. | ||
| 650 | 4 | |a Immune checkpoint inhibition | |
| 650 | 4 | |a Melanoma | |
| 650 | 4 | |a mutation | |
| 650 | 4 | |a Mutational analysis | |
| 650 | 4 | |a Systemic treatment | |
| 650 | 4 | |a Targeted therapy | |
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