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Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway

Alternative splicing plays a pivotal role in tumorigenesis and proliferation. However, its pattern and pathogenic role has not been systematically analyzed in multiple myeloma or its subtypes. Alternative splicing profiles for 598 newly diagnosed myeloma patients with comprehensive genomic annotatio...

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Autores principales: Liu, Enze, Becker, Nathan, Sudha, Parvathi, Dong, Chuanpeng, Liu, Yunlong, Keats, Jonathan, Morgan, Gareth, Walker, Brian A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859791/
https://www.ncbi.nlm.nih.gov/pubmed/36670103
http://dx.doi.org/10.1038/s41408-023-00783-0
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author Liu, Enze
Becker, Nathan
Sudha, Parvathi
Dong, Chuanpeng
Liu, Yunlong
Keats, Jonathan
Morgan, Gareth
Walker, Brian A.
author_facet Liu, Enze
Becker, Nathan
Sudha, Parvathi
Dong, Chuanpeng
Liu, Yunlong
Keats, Jonathan
Morgan, Gareth
Walker, Brian A.
author_sort Liu, Enze
collection PubMed
description Alternative splicing plays a pivotal role in tumorigenesis and proliferation. However, its pattern and pathogenic role has not been systematically analyzed in multiple myeloma or its subtypes. Alternative splicing profiles for 598 newly diagnosed myeloma patients with comprehensive genomic annotation identified primary translocations, 1q amplification, and DIS3 events to have more differentially spliced events than those without. Splicing levels were correlated with expression of splicing factors. Moreover, the non-homologous end joining pathway was an independent factor that was highly associated with splicing frequency as well as an increased number of structural variants. We therefore identify an axis of high-risk disease encompassing expression of the non-homologous end joining pathway, increase structural variants, and increased alternative splicing that are linked together. This indicates a joint pathogenic role for DNA damage response and alternative RNA processing in myeloma.
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spelling pubmed-98597912023-01-22 Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway Liu, Enze Becker, Nathan Sudha, Parvathi Dong, Chuanpeng Liu, Yunlong Keats, Jonathan Morgan, Gareth Walker, Brian A. Blood Cancer J Article Alternative splicing plays a pivotal role in tumorigenesis and proliferation. However, its pattern and pathogenic role has not been systematically analyzed in multiple myeloma or its subtypes. Alternative splicing profiles for 598 newly diagnosed myeloma patients with comprehensive genomic annotation identified primary translocations, 1q amplification, and DIS3 events to have more differentially spliced events than those without. Splicing levels were correlated with expression of splicing factors. Moreover, the non-homologous end joining pathway was an independent factor that was highly associated with splicing frequency as well as an increased number of structural variants. We therefore identify an axis of high-risk disease encompassing expression of the non-homologous end joining pathway, increase structural variants, and increased alternative splicing that are linked together. This indicates a joint pathogenic role for DNA damage response and alternative RNA processing in myeloma. Nature Publishing Group UK 2023-01-20 /pmc/articles/PMC9859791/ /pubmed/36670103 http://dx.doi.org/10.1038/s41408-023-00783-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Enze
Becker, Nathan
Sudha, Parvathi
Dong, Chuanpeng
Liu, Yunlong
Keats, Jonathan
Morgan, Gareth
Walker, Brian A.
Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway
title Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway
title_full Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway
title_fullStr Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway
title_full_unstemmed Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway
title_short Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway
title_sort alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859791/
https://www.ncbi.nlm.nih.gov/pubmed/36670103
http://dx.doi.org/10.1038/s41408-023-00783-0
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