Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wiesner, T; He, J; Yelensky, R; Esteve-Puig, R; Botton, T; Yeh, I; Lipson, D; Otto, G; Brennan, K; Murali, R; Garrido, M; Miller, VA; Ross, JS; Berger, MF; Sparatta, A; Palmedo, G; Cerroni, L; Busam, KJ; Kutzner, H; Cronin, MT; Stephens, PJ; Bastian, BC.
Kinase fusions are frequent in Spitz tumours and spitzoid melanomas.
Nat Commun. 2014; 5(5):3116-3116
Doi: 10.1038/ncomms4116
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- Führende Autor*innen der Med Uni Graz
- Wiesner Thomas
- Co-Autor*innen der Med Uni Graz
- Cerroni Lorenzo
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- Abstract:
- Spitzoid neoplasms are a group of melanocytic tumours with distinctive histopathological features. They include benign tumours (Spitz naevi), malignant tumours (spitzoid melanomas) and tumours with borderline histopathological features and uncertain clinical outcome (atypical Spitz tumours). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbour kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%) and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signalling pathways, are tumourigenic and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz naevi, 56% of atypical Spitz tumours and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signalling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanomas.
- Find related publications in this database (using NLM MeSH Indexing)
- Base Sequence -
- DNA Mutational Analysis -
- Genome, Human -
- Humans -
- Melanoma - metabolism
- Melanoma - pathology
- Molecular Sequence Data -
- Nevus, Epithelioid and Spindle Cell - metabolism
- Nevus, Epithelioid and Spindle Cell - pathology
- Oncogene Proteins, Fusion - metabolism
- Protein Kinases - metabolism
- Reproducibility of Results -
- Skin Neoplasms - metabolism
- Skin Neoplasms - pathology
- Xenograft Model Antitumor Assays -