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The relation between c-myc expression and interferon sensitivity in uveal melanoma
P N Tulley1, M Neale, D Jackson
1RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, UK. paultulley@hotmail.com
Background/Aim:
Interferons (IFN) are currently being used to treat melanoma, including some patients with uveal melanoma. IFN is thought to inhibit tumour growth through downregulation of the c-myc oncogene; the overexpression of which has been shown to be associated with resistance in cell lines. The aim of this study was to investigate the relation between c-myc gene expression and IFN sensitivity in a series of uveal melanomas in a short term chemosensitivity assay.
Methods:
Tumours from 45 patients with uveal melanoma who had undergone enucleation were studied. The ATP chemosensitivity assay was used to study sensitivity to IFN-alpha-2b in freshly isolated cells from each tumour. Flow cytometry was used to assess c-myc expression in formalin fixed material from the primary specimens.
Results:
There was a wide range of IFN sensitivity between the specimens whereas c-myc expression was universal and present in 80% of the tumour cells in 80% of the specimens. Higher c-myc expression was associated with IFN-alpha resistance as measured by the maximum percentage of inhibition (p = 0.05) and there was a trend with the IFN sensitivity index (p = 0.07).
Conclusions:
These results demonstrate that tumours with high c-myc expression are also associated with IFN resistance. Future research is required to explore the potential of c-myc gene manipulation combined with IFN therapy.
Insights
High c-myc gene expression in uveal melanoma tumors correlates with resistance to interferon (IFN) therapy. This suggests c-myc manipulation could enhance IFN treatment effectiveness for this eye cancer.
Area of Science:
- Oncology
- Ophthalmology
- Molecular Biology
Background:
- Interferons (IFN) are used to treat melanoma, including uveal melanoma.
- IFN is believed to inhibit tumor growth by downregulating the c-myc oncogene.
- c-myc overexpression is linked to treatment resistance in cell lines.
Purpose of the Study:
- To investigate the relationship between c-myc gene expression and interferon sensitivity in uveal melanoma.
- To assess the role of c-myc in predicting treatment response.
Main Methods:
- Analyzed tumors from 45 uveal melanoma patients.
- Utilized an ATP chemosensitivity assay for IFN-alpha-2b sensitivity.
- Employed flow cytometry to measure c-myc expression.
Main Results:
- Observed a broad range of IFN sensitivity across specimens.
- Found universal c-myc expression in 80% of tumors.
- Demonstrated that higher c-myc expression is associated with IFN-alpha resistance (p=0.05).
Conclusions:
- Tumors with elevated c-myc expression exhibit resistance to IFN therapy.
- Further research into c-myc gene manipulation alongside IFN therapy is warranted.

