Holding on to junk bonds: intron retention in cancer and therapy

Monteuuis, Geoffray, Schmitz, Ulf, Petrova, Veronika, Kearney, Padraic S., and Rasko, John E.J. (2020) Holding on to junk bonds: intron retention in cancer and therapy. Cancer Research, 81 (4). pp. 779-789.

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Abstract

Intron retention (IR) in cancer was for a long time overlooked by the scientific community, as it was previously considered to be an artifact of a dysfunctional spliceosome. Technological advancements made in the last decade offer unique opportunities to explore the role of IR as a widespread phenomenon that contributes to the transcriptional diversity of many cancers. Numerous studies in cancer have shed light on dysregulation of cellular mechanisms that lead to aberrant and pathologic IR. IR is not merely a mechanism of gene regulation, but rather it can mediate cancer pathogenesis and therapeutic resistance in various human diseases. The burden of IR in cancer is governed by perturbations to mechanisms known to regulate this phenomenon and include epigenetic variation, mutations within the gene body, and splicing factor dysregulation. This review summarizes possible causes for aberrant IR and discusses the role of IR in therapy or as a consequence of disease treatment. As neoepitopes originating from retained introns can be presented on the cancer cell surface, the development of personalized cancer vaccines based on IR-derived neoepitopes should be considered. Ultimately, a deeper comprehension about the origins and consequences of aberrant IR may aid in the development of such personalized cancer vaccines.

Item ID: 68809
Item Type: Article (Research - C1)
ISSN: 1538-7445
Copyright Information: (C) 2020 American Association for Cancer Research
Funders: National Health and Medical Research Council of Australia (NHMRC), Cancer Council NSW
Projects and Grants: NHMRC Investigator Grant #1177305, NHMRC Project Grant #1080530, NHMRC Project Grant #1061906, NHMRC Project Grant #112817, NHMRC Project Grant #112990, CC G11-12, CC RG14-09, CC RG20-12
Date Deposited: 17 Aug 2021 01:34
FoR Codes: 31 BIOLOGICAL SCIENCES > 3105 Genetics > 310505 Gene expression (incl. microarray and other genome-wide approaches) @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321103 Cancer genetics @ 50%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 20%
28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 80%
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