Elfman Justin, Pham Lam-Phong, Li Hui
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, 22904 USA.
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22904 USA.
J Genet Genomics. 2020 Jul 20;47(7):341-348. doi: 10.1016/j.jgg.2020.04.005. Epub 2020 Jun 14.
Gene fusions have long been considered hallmarks of cancer. Efforts into characterization of their prevalence, cause, and function have provided significant progress toward improvements in diagnosis, prognosis assessment, and treatment of numerous cancers. More recently, detection of intergenically spliced chimeric RNAs in cancer have spurred efforts to characterize these transcripts, anticipating similar successes in translation to the clinic. Discovery of chimeric RNAs in normal cells, especially those which precede canonical translocations such as and , suggest that these physiologically-regulated transcripts may function as proto-oncogenic factors, in that their dysregulation can lead to cancer progression. These findings have given rise to conjecture regarding chimeric RNA-guided rearrangements giving rise to fusion genes, termed The Cart Before The Horse Hypothesis. Here, we provide context for the relationship between gene fusions, chimeric RNAs, and cancer, assemble evidence in support of the Cart Before The Horse Hypothesis, and discuss potential advantages of targeting chimeric RNAs in cancer treatment.
基因融合长期以来一直被视为癌症的标志。对其发生率、成因和功能的研究已在改善多种癌症的诊断、预后评估和治疗方面取得了重大进展。最近，在癌症中检测到基因间剪接的嵌合RNA，这促使人们努力对这些转录本进行表征，期望在临床转化方面取得类似的成功。在正常细胞中发现嵌合RNA，尤其是那些先于典型易位（如 和 ）的嵌合RNA，表明这些受生理调节的转录本可能作为原癌基因发挥作用，因为它们的失调会导致癌症进展。这些发现引发了关于嵌合RNA引导的重排产生融合基因的推测，即“本末倒置假说”。在此，我们阐述了基因融合、嵌合RNA与癌症之间的关系，收集了支持“本末倒置假说”的证据，并讨论了在癌症治疗中靶向嵌合RNA的潜在优势。
