Gene Fusion in Malignant Glioma: An Emerging Target for Next-Generation Personalized Treatment Tao Xu, Hongxiang Wang, Xiaoquan Huang, Weiqing Li, Qilin.

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Presentation transcript:

Gene Fusion in Malignant Glioma: An Emerging Target for Next-Generation Personalized Treatment Tao Xu, Hongxiang Wang, Xiaoquan Huang, Weiqing Li, Qilin Huang, Yong Yan, Juxiang Chen Translational Oncology Volume 11, Issue 3, Pages 609-618 (June 2018) DOI: 10.1016/j.tranon.2018.02.020 Copyright © 2018 The Authors Terms and Conditions

Figure 1 Gene fusions leading to chimeric transcripts through a variety of mechanisms. Fusion genes can form at chromosomal level, where translocation, insertion, inversion, and deletion occur and produce B-A and A-B fusion mRNAs, A-B fusion mRNA, C-D fusion mRNA, and E-F fusion mRNA, respectively. Fusion transcripts can also be caused by trans-splicing (G-H fusion mRNA) or cis-splicing (I-J fusion mRNA) events at posttranscriptional level. Black blocks represent introns. Cyan block in the pre-mRNA represents intergenic region. Translational Oncology 2018 11, 609-618DOI: (10.1016/j.tranon.2018.02.020) Copyright © 2018 The Authors Terms and Conditions

Figure 2 FGFR3-TACC3 fusion-mediated oncogenic pathways in GBM. FGFR3-TACC3 protein can constitutively and automatically activate tyrosine kinase domain, which exerts oncogenic function weakly through PI3K/ATK, RAS/MAPK, and STAT3 signaling and may localize to mitotic spindle poles to trigger aneuploidy. Translational Oncology 2018 11, 609-618DOI: (10.1016/j.tranon.2018.02.020) Copyright © 2018 The Authors Terms and Conditions

Figure 3 Overview of downstream signaling linked to selected driver fusions and potential intervention of specific targeting inhibitors. Glioma-associated oncogenic fusion proteins commonly activate canonical pathways, such as JAK/STAT3, ERK/MAKP, PI3K/ATK, and NF-κB, involved in tumor survival, proliferation, and tumorigenesis. Some of the proteins have been explored as therapeutic targets to inhibit glioma. Translational Oncology 2018 11, 609-618DOI: (10.1016/j.tranon.2018.02.020) Copyright © 2018 The Authors Terms and Conditions