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Updated: May 9, 2026
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Gene fusions in melanocytic lesions: an updated comprehensive review
Volha Lenskaya1, Larisa Erikson2, Victor G Prieto1
1Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
The scope of gene fusions in melanocytic neoplasms is broader than previously recognized, extending well beyond the Spitz-lineage neoplasms where kinase fusions involving ALK, ROS1, NTRK1/2/3, RET, MET, BRAF, and MAP3K8 define biologically and morphologically distinct tumors. Emerging studies demonstrate that a meaningful proportion of conventional non-Spitz lineage melanomas harbor oncogenic fusions. Such fusions may impact clinical behavior, histopathologic presentation and provide opportunities for targeted therapy. The World Health Organization classification of skin tumors, 5th edition, now incorporates fusion status into taxonomy and risk stratification, yet some important questions remain for further investigation: fusion-associated neoplasms can mimic non-melanocytic neoplasm; Spitz-type fusions appear in non-Spitz lesions; and melanocytic differentiation may occur in some other fusion-driven lesions. Broad-panel next-generation sequencing (including RNAseq), together with targeted fluorescence in situ hybridization and immunohistochemistry enhances detection of known and novel fusion partners. Early clinical evidence of TRK, ALK, and ROS1 inhibitor efficacy underscores the translational promise of fusion testing and opens avenues for personalized therapy. This review synthesizes current knowledge on the genomics, histopathology, diagnosis, and therapeutic implications of fusion-driven melanocytic neoplasms, highlighting consensus points and remaining controversies.
Insights
Gene fusions are more common in melanocytic neoplasms than previously thought, impacting tumor behavior and offering targeted therapy options. These genetic alterations are increasingly recognized in various melanoma types, guiding diagnosis and treatment.
Area of Science:
- Oncology
- Genetics
- Dermatopathology
Background:
- Kinase gene fusions are established drivers in Spitz-lineage neoplasms.
- Emerging evidence reveals oncogenic fusions in conventional non-Spitz melanomas.
- Fusion status is now integrated into the World Health Organization classification of skin tumors.
Purpose of the Study:
- To review the expanding role of gene fusions in melanocytic neoplasms.
- To discuss the diagnostic and therapeutic implications of these fusions.
- To highlight current knowledge gaps and future research directions.
Main Methods:
- Comprehensive literature review of studies on gene fusions in melanocytic neoplasms.
- Analysis of genomic, histopathologic, and clinical data.
- Synthesis of information on detection methods and therapeutic strategies.
Main Results:
- Gene fusions are found in a broader range of melanocytic tumors than previously recognized.
- These fusions influence tumor biology, histopathology, and clinical behavior.
- Targeted therapies show promise, with early efficacy noted for TRK, ALK, and ROS1 inhibitors.
Conclusions:
- Gene fusions represent a significant and expanding category of driver alterations in melanocytic neoplasms.
- Accurate detection via next-generation sequencing and other methods is crucial for diagnosis and personalized treatment.
- Further research is needed to address diagnostic challenges and fully elucidate the therapeutic potential.
