Tuna Musaffe, Amos Christopher I, Mills Gordon B
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Oncotarget. 2019 Mar 12;10(21):2095-2111. doi: 10.18632/oncotarget.26777.
Recurrent fusion transcripts, which are one of the characteristic hallmarks of cancer, arise either from chromosomal rearrangements or from transcriptional errors in splicing. DNA rearrangements include intrachromosomal or interchromosomal translocation, tandem duplication, deletion, inversion, or result from chromothripsis, which causes complex rearrangements. In addition, fusion proteins can be created through transcriptional read-through. Fusion genes can be transcribed to fusion transcripts and translated to chimeric proteins, with many having demonstrated transforming activities through multiple mechanisms in cells. Fusion proteins represent novel therapeutic targets and diagnostic biomarkers of diagnosis, disease status, or progression. This review focuses on the mechanisms underlying the formation of oncogenic fusion genes and transcripts and their impact on the pathobiology of epithelial tumors.
复发性融合转录本是癌症的特征性标志之一,其产生要么源于染色体重排,要么源于剪接过程中的转录错误。DNA重排包括染色体内或染色体间易位、串联重复、缺失、倒位,或者由染色体碎裂导致,后者会引起复杂的重排。此外,融合蛋白可通过转录通读产生。融合基因可转录为融合转录本并翻译为嵌合蛋白,其中许多已通过多种细胞机制表现出转化活性。融合蛋白代表了新型治疗靶点以及诊断、疾病状态或病情进展的诊断生物标志物。本综述重点关注致癌融合基因和转录本形成的潜在机制及其对上皮性肿瘤病理生物学的影响。