Venables Julian P
University of Newcastle-upon-Tyne, Institute of Human Genetics, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, UK.
Bioessays. 2006 Apr;28(4):378-86. doi: 10.1002/bies.20390.
Alternative pre-mRNA splicing leads to distinct products of gene expression in development and disease. Antagonistic splice variants of genes involved in differentiation, apoptosis, invasion and metastasis often exist in a delicate equilibrium that is found to be perturbed in tumours. In several recent examples, splice variants that are overexpressed in cancer are expressed as hyper-oncogenic proteins, which often correlate with poor prognosis, thus suggesting improved diagnosis and follow up treatment. Global gene expression technologies are just beginning to decipher the interplay between alternatively spliced isoforms and protein-splicing factors that will lead to identification of the mutations in these trans-acting factors responsible for pathogenic alternative splicing in cancer.
可变前体mRNA剪接在发育和疾病过程中导致基因表达产生不同的产物。参与分化、凋亡、侵袭和转移的基因的拮抗剪接变体通常处于一种微妙的平衡状态，而这种平衡在肿瘤中会被打破。在最近的几个例子中，在癌症中过度表达的剪接变体被表达为高致癌蛋白，这通常与不良预后相关，因此提示可改善诊断和后续治疗。全球基因表达技术刚刚开始解读可变剪接异构体与蛋白质剪接因子之间的相互作用，这将有助于识别这些反式作用因子中的突变，这些突变是癌症中致病性可变剪接的原因。
