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Beyond chromosomal rearrangements: The expanding landscape of gene fusions and chimeric RNAs

Sangeen Khan1,2† ,  Yue Tang1,2† ,  Zhenguo Song1,2,3 ,  Xi Chen4 ,  Lijun Wang5 ,  Chengjuan Zhang6 ,  Fujun Qin1,2*
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1 Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China
2 Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
3 Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China
4 Department of Cardiovascular, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
5 Departement of Nuclear Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China
6 Center of Bio-Repository, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China
GPD, 3641 https://doi.org/10.36922/gpd.3641
Submitted: 12 May 2024 | Accepted: 26 August 2024 | Published: 28 October 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

BCR–ABL, the pioneering gene fusion resulting from chromosomal translocation, has marked a major milestone in understanding genetic alterations in cancer. Initially, gene fusions were linked solely to chromosomal rearrangements, serving as diagnostic markers and cancer drivers. However, advancements in high-throughput sequencing and bioinformatics have revealed additional mechanisms underlying gene fusion. The term “gene fusion” primarily refers to fusion events at the DNA level, whereas “chimeric RNA” encompasses a wide range of transcripts containing exons from different parental genes, including gene fusion transcripts. Recent developments have identified numerous chimeric RNAs in various cancer types, extending even to non-cancerous tissues. Chimeric RNAs, originating from events such as trans-splicing, read-through, and intergenic splicing, form a complex landscape with varied functions. While some chimeric RNAs have defined roles and therapeutic potential, a comprehensive understanding of their diverse functions remains a priority. Exploring the full spectrum of chimeric RNA activities is crucial for revealing their clinical and therapeutic implications. In addition, chimeric RNAs are key players in tumorigenesis, affecting cellular processes, and driving cancer progression. Understanding their intricate interactions with cellular pathways is essential for developing targeted therapies and precision medicine approaches. The dynamic nature of chimeric RNAs highlights the need for ongoing research to fully harness their diagnostic and therapeutic potential.

Keywords
Chimeric RNA
Gene fusion
Splicing
Cis-splicing
Trans-splicing
Cis-SAGe
Cancer
Funding
F.Q. was supported by the National Natural Science Foundation of China (No.81972421) and Joint Program NSFC-Henan (No.U2004135); Y.T. was supported by the Education and Teaching Reform Research and the Practice Project for international students at ZZU (2022ZZUJGXMLXS-017); L.W. was supported by the Henan Province Medical Science and Technology Research Project (LHGJ20210208); Z.S. was supported by the Program for Tackling Key Problems of Henan Department of Science and Technology (No.202102310033) and the Henan Province Medical Science and Technology Research Project (LHGJ20210191); C.Z. was supported by the Henan Provincial Young and Middle-aged Health Science and Technology Innovation Talent Project (YXKC2021032) and the Zhengzhou University Young Teachers Basic Research Training Project (JC23858081).
Conflict of interest
Fujun Qin is an Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
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