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Updated: Jun 2, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Tumour heterogeneity of mucosal melanomas during treatment with imatinib
N L Schoenewolf1, M Urosevic-Maiwald, R Dummer
1Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland.
Abstract:
A comparison of in vitro and in vivo characteristics of tumour cells derived from patients with mucosal melanoma treated with imatinib was performed with respect to KIT mutations. Three patients with mucosal melanoma were treated with imatinib. Patient-derived tumour material was used to establish melanoma cell cultures ex vivo. We evaluated tumour material and cell cultures for KIT protein expression and KIT mutation status. In addition, proliferation assays with melanoma cell cultures were performed with imatinib. Expression of KIT protein and KIT mutation was shown in two patients who responded to imatinib in vivo. Cells derived from a third patient who did not respond to imatinib did not express KIT and lacked a KIT mutation. Patient-derived melanoma cells did not show any KIT mutations, nor did they respond to imatinib in vitro. Our study underlines that melanoma consists of a heterogeneous cell population, making it imperative to use the mapping of involved activating tumour growth-driving pathways in order to improve response to therapy with kinase inhibitors.
Insights
This study investigated imatinib treatment in mucosal melanoma, finding that KIT mutations and expression correlated with patient response. Tumour cells lacking KIT mutations did not respond to imatinib in vitro, highlighting melanoma heterogeneity.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Mucosal melanoma is a rare and aggressive subtype of melanoma.
- Imatinib is a tyrosine kinase inhibitor targeting KIT, often mutated in various cancers.
- Understanding KIT mutation status is crucial for predicting response to imatinib therapy.
Observation:
- Three patients with mucosal melanoma were treated with imatinib.
- Patient-derived tumour cells were cultured ex vivo to assess KIT expression and mutation status.
- In vitro proliferation assays were conducted using imatinib on melanoma cell cultures.
Findings:
- Two patients who responded to imatinib in vivo showed KIT protein expression and KIT mutations.
- A non-responding patient's tumour lacked KIT expression and mutations.
- Patient-derived melanoma cells did not exhibit KIT mutations and were unresponsive to imatinib in vitro.
Implications:
- Melanoma exhibits significant cellular heterogeneity.
- Targeting specific activating tumour growth pathways is essential for improving kinase inhibitor therapy response.
- KIT mutation analysis is critical for guiding imatinib treatment in mucosal melanoma.
