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The emerging complexity of gene fusions in cancer

Abstract

Structural chromosome rearrangements may result in the exchange of coding or regulatory DNA sequences between genes. Many such gene fusions are strong driver mutations in neoplasia and have provided fundamental insights into the disease mechanisms that are involved in tumorigenesis. The close association between the type of gene fusion and the tumour phenotype makes gene fusions ideal for diagnostic purposes, enabling the subclassification of otherwise seemingly identical disease entities. In addition, many gene fusions add important information for risk stratification, and increasing numbers of chimeric proteins encoded by the gene fusions serve as specific targets for treatment, resulting in dramatically improved patient outcomes. In this Timeline article, we describe the spectrum of gene fusions in cancer and how the methods to identify them have evolved, and also discuss conceptual implications of current, sequencing-based approaches for detection.

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Figure 1: Major discoveries from research on gene fusions and cancer.
Figure 2: The chromosomal basis of gene fusions.
Figure 3: Gene fusion networks in AML.
Figure 4: Gene fusion reports.
Figure 5: Gene fusion networks in ovarian cancer.

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Acknowledgements

The authors would like to acknowledge financial support from the Swedish Cancer Society, the Swedish Research Council and the Swedish Childhood Cancer Foundation.

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Mertens, F., Johansson, B., Fioretos, T. et al. The emerging complexity of gene fusions in cancer. Nat Rev Cancer 15, 371–381 (2015). https://doi.org/10.1038/nrc3947

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