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    Driver Fusions and Their Implications in the Development and Treatment of Human Cancers

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    Author
    Gao, Q; Liang, W-W; Foltz, SM; Mutharasu, G; Jayasinghe, RG; Cao, S; Liao, W-W; Reynolds, SM; Wyczalkowski, MA; Yao, L; ...
    Date
    2018-04-03
    Source Title
    Cell Reports
    Publisher
    CELL PRESS
    University of Melbourne Author/s
    Boussioutas, Alex; Corcoran, Niall; Hovens, Christopher; Costello, Anthony
    Affiliation
    Surgery (RMH)
    Medicine and Radiology
    Metadata
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    Document Type
    Journal Article
    Citations
    Gao, Q., Liang, W. -W., Foltz, S. M., Mutharasu, G., Jayasinghe, R. G., Cao, S., Liao, W. -W., Reynolds, S. M., Wyczalkowski, M. A., Yao, L., Yu, L., Sun, S. Q., Chen, K., Lazar, A. J., Fields, R. C., Wendl, M. C., Van Tine, B. A., Vij, R., Chen, F. ,... Ding, L. (2018). Driver Fusions and Their Implications in the Development and Treatment of Human Cancers. CELL REPORTS, 23 (1), pp.227-+. https://doi.org/10.1016/j.celrep.2018.03.050.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254789
    DOI
    10.1016/j.celrep.2018.03.050
    Abstract
    Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy.

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