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Updated: Mar 11, 2026
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Kinase gene fusions in defined subsets of melanoma
Jacqueline Turner1, Kasey Couts1, Jamie Sheren1
1Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, CO, USA.
Abstract:
Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by Immunohistochemistry (IHC) or sequencing and one was found to be an ARMC10-BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought and should be further explored particularly in melanomas lacking known driver mutations.
Insights
Genomic rearrangements forming kinase fusions are found in melanoma subtypes. Researchers identified a novel ARMC10-BRAF fusion, suggesting gene fusions are more common in melanomas lacking known driver mutations.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Activating kinase fusions are increasingly recognized in various cancers.
- The frequency of these genomic rearrangements in specific melanoma subtypes remains largely unreported.
Purpose of the Study:
- To investigate the occurrence of genomic rearrangements leading to kinase fusions in diverse malignant melanoma subtypes.
- To identify novel gene fusions in melanoma, particularly in tumors without known driver mutations.
Main Methods:
- Break-apart fluorescence in situ hybridization (FISH) was employed to detect genomic rearrangements.
- Immunohistochemistry (IHC) and gene sequencing were used for confirmation of identified fusions.
Main Results:
- Four genomic rearrangements involving BRAF, RET, and ROS1 genes were identified in 59 melanoma tissue samples.
- A previously unreported ARMC10-BRAF fusion was discovered in a melanoma subtype.
- These fusions were observed in melanomas lacking common driver mutations.
Conclusions:
- Gene fusions may be more prevalent in melanoma than previously assumed.
- Further investigation of gene fusions is warranted, especially in melanomas lacking established driver mutations.
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