Surgery and Cancer, Imperial College London, London, UK.
Metabolism, Digestion and Reproduction, Imperial College London, London, UK
J Med Genet. 2021 Dec;58(12):789-795. doi: 10.1136/jmedgenet-2021-108010. Epub 2021 Aug 30.
Gene fusion, a genomic event that generates a novel gene from two independent genes, has long been known to be implicated in tumourigenesis and cancer progression. It has thus served as a diagnostic and prognostic biomarker in cancer, as well as an ideal therapeutic target in cancer therapy. Gene fusion can arise from chromosomal rearrangement and alternative splicing of transcripts, resulting in deregulation of proto-oncogenes or creation of an oncogenic novel gene. Largely facilitated by next generation sequencing technologies, a plethora of novel gene fusions have been identified in a variety of cancers, which leaves us the challenge of functionally characterising these candidate gene fusions. In this review, we summarise the molecular mechanisms, the oncogenic consequences and the therapeutic implications of verified gene fusions. We also discuss recent studies on gene fusions in both common and rare subtypes of ovarian tumours and how these findings can be translated to cancer therapies to benefit patients carrying these gene fusions.
基因融合是一种从两个独立基因中产生新基因的基因组事件，长期以来一直被认为与肿瘤发生和癌症进展有关。因此，它已成为癌症诊断和预后的生物标志物，也是癌症治疗中理想的治疗靶点。基因融合可源于染色体重排和转录本的选择性剪接，导致原癌基因失调控或产生致癌新基因。在下一代测序技术的大力推动下，在各种癌症中发现了大量新的基因融合，这给我们带来了功能表征这些候选基因融合的挑战。在这篇综述中，我们总结了已验证的基因融合的分子机制、致癌后果和治疗意义。我们还讨论了卵巢肿瘤常见和罕见亚型中基因融合的最新研究，以及这些发现如何转化为癌症治疗，使携带这些基因融合的患者受益。
