Gene fusions are an important class of mutations in several cancer types and include genomic rearrangements that fuse regulatory or coding elements from two different genes. Analysis of the genetics of cancers harboring fusion oncogenes and the proteins they encode have enhanced cancer diagnosis and in some cases patient treatment. However, the effect of the complex structure of fusion genes on the biogenesis of the resulting chimeric transcripts they express is not well studied. There are two potential RNA-related vulnerabilities inherent to fusion-driven cancers: (a) the processing of the fusion precursor messenger RNA (pre-mRNA) to the mature mRNA and (b) the mature mRNA. In this study, we discuss the effects that the genetic organization of fusion oncogenes has on the generation of translatable mature RNAs and the diversity of fusion transcripts expressed in different cancer subtypes, which can fundamentally influence both tumorigenesis and treatment. We also discuss functional genomic approaches that can be utilized to identify proteins that mediate the processing of fusion pre-mRNAs. Furthermore, we assert that an enhanced understanding of fusion transcript biogenesis and the diversity of the chimeric RNAs present in fusion-driven cancers will increase the likelihood of successful application of RNA-based therapies in this class of tumors. This article is categorized under: RNA Processing > RNA Editing and Modification RNA Processing > Splicing Regulation/Alternative Splicing RNA in Disease and Development > RNA in Disease.

中文翻译：

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融合转录本：未利用的癌症脆弱性？

基因融合是几种癌症类型中重要的一类突变，包括融合来自两个不同基因的调控或编码元件的基因组重排。带有融合癌基因的癌症的遗传学分析及其编码的蛋白质增强了癌症的诊断，在某些情况下还提高了患者的治疗能力。但是，融合基因的复杂结构对其表达的嵌合转录本的生物发生的影响尚未得到很好的研究。融合驱动的癌症固有的两个潜在的与RNA相关的脆弱性：（a）将融合前体信使RNA（pre-mRNA）加工成成熟的mRNA，以及（b）成熟的mRNA。在这个研究中，我们讨论了融合致癌基因的遗传组织对可翻译成熟RNA的产生以及在不同癌症亚型中表达的融合转录本多样性的影响，这可以从根本上影响肿瘤发生和治疗。我们还讨论了可用于鉴定介导融合前mRNA加工的蛋白质的功能基因组学方法。此外，我们断言，对融合转录物的生物发生以及融合驱动的癌症中存在的嵌合RNA的多样性的加深了解，将增加在此类肿瘤中成功应用基于RNA的疗法的可能性。本文归类于：RNA加工> RNA编辑和修饰RNA加工>疾病和发育中的剪接调控/替代剪接RNA>