Oncotarget

Reviews:

Molecular mechanisms and pathobiology of oncogenic fusion transcripts in epithelial tumors

Musaffe Tuna _, Christopher I. Amos and Gordon B. Mills

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Oncotarget. 2019; 10:2095-2111. https://doi.org/10.18632/oncotarget.26777

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Abstract

Musaffe Tuna1,2, Christopher I. Amos2,3 and Gordon B. Mills4,5,6

1Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2Department of Medicine, Baylor College of Medicine, Houston, TX, USA

3Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA

4Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

5Department of Cell, Developmental and Cancer Biology, School of Medicine, Oregon Health Science University, Portland, OR, USA

6Precision Oncology, Knight Cancer Institute, Portland, OR, USA

Correspondence to:

Musaffe Tuna, email: [email protected]

Keywords: fusion genes; fusion transcripts; epithelial tumors; mechanisms; pathobiology

Received: November 14, 2018     Accepted: February 22, 2019     Published: March 12, 2019

ABSTRACT

Recurrent fusion transcripts, which are one of the characteristic hallmarks of cancer, arise either from chromosomal rearrangements or from transcriptional errors in splicing. DNA rearrangements include intrachromosomal or interchromosomal translocation, tandem duplication, deletion, inversion, or result from chromothripsis, which causes complex rearrangements. In addition, fusion proteins can be created through transcriptional read-through. Fusion genes can be transcribed to fusion transcripts and translated to chimeric proteins, with many having demonstrated transforming activities through multiple mechanisms in cells. Fusion proteins represent novel therapeutic targets and diagnostic biomarkers of diagnosis, disease status, or progression. This review focuses on the mechanisms underlying the formation of oncogenic fusion genes and transcripts and their impact on the pathobiology of epithelial tumors.


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