Carling Phillippa J, Elliott David J, Robson Craig N, Leung Hing Y, Rajan Prabhakar
Institute of Human Genetics, Newcastle University, Newcastle NE1 7RU, United Kingdom.
Discov Med. 2009 Aug;8(41):74-80.
Prostate cancer is the most common cancer seen in aging males in the Western world, and is a major clinical challenge in uro-oncology due to biological heterogeneity. Recent advances in molecular medicine suggest that the genetic composition of a prostate tumor contributes significantly to the complexity of the disease. An important genetic mechanism underlying biological diversity is alternative pre-mRNA splicing, which is thought to affect approximately 95% of transcripts derived from protein-encoding genes. During alternative splicing, coding (exons) and non-coding (introns) regions of pre-messenger RNA (pre-mRNA) transcripts derived from a single gene are rearranged to generate several mRNAs species, which are translated into distinct protein isoforms with differing biological functions. Recent emerging evidence suggests that prostate cancer-specific aberrant and alternative splicing may contribute to the biological heterogeneity of the disease. Furthermore, identification of prostate cancer-specific splice variants may yield novel biomarkers and targets for therapy to improve patient care and clinical outcome.
前列腺癌是西方世界老年男性中最常见的癌症，由于其生物学异质性，它是泌尿肿瘤学中的一项重大临床挑战。分子医学的最新进展表明，前列腺肿瘤的基因组成对该疾病的复杂性有显著影响。生物多样性背后的一个重要遗传机制是前体mRNA可变剪接，据认为它影响约95%的蛋白质编码基因转录本。在可变剪接过程中，来自单个基因的信使核糖核酸前体（pre-mRNA）转录本的编码（外显子）和非编码（内含子）区域会重新排列，以产生几种mRNA种类，它们被翻译成具有不同生物学功能的不同蛋白质异构体。最近出现的证据表明，前列腺癌特异性异常和可变剪接可能导致该疾病的生物学异质性。此外，鉴定前列腺癌特异性剪接变体可能会产生新的生物标志物和治疗靶点，以改善患者护理和临床结果。
