a Department of Cell and Developmental Biology , University of British Columbia , Vancouver , BC , Canada.
b Michael Cuccione Childhood Cancer Research Program , BC Children's Hospital Research Institute , Vancouver , BC , Canada.
Expert Rev Proteomics. 2019 Mar;16(3):185-200. doi: 10.1080/14789450.2019.1575206. Epub 2019 Feb 18.
Cancer changes the proteome in complex ways that reach well beyond simple changes in protein abundance. Genomic and transcriptional variations and post-translational protein modification create functional variants of a protein, known as proteoforms. Childhood cancers have fewer genomic alterations but show equally dramatic phenotypic changes as malignant cells in adults. Therefore, unraveling the complexities of the proteome is even more important in pediatric malignancies. Areas covered: In this review, the biological origins of proteoforms and technological advancements in the study of proteoforms are discussed. Particular emphasis is given to their implication in childhood malignancies and the critical role of cancer-specific proteoforms for the next generation of cancer therapies and diagnostics. Expert opinion: Recent advancements in technology have led to a better understanding of the underlying mechanisms of tumorigenesis. This has been critical for the development of more effective and less harmful treatments that are based on direct targeting of altered proteins and deregulated pathways. As proteome coverage and the ability to detect complex proteoforms increase, the most need for change is in data compilation and database availability to mediate high-level data analysis and allow for better functional annotation of proteoforms.
癌症以复杂的方式改变蛋白质组，远远超出了蛋白质丰度的简单变化。基因组和转录组的变异以及翻译后蛋白质修饰产生了蛋白质的功能变体，称为蛋白质异构体。儿童癌症的基因组改变较少，但与成人恶性细胞一样，表现出同样剧烈的表型变化。因此，在儿科恶性肿瘤中，揭示蛋白质组的复杂性更为重要。
在这篇综述中，讨论了蛋白质异构体的生物学起源和研究蛋白质异构体的技术进展。特别强调了它们在儿童恶性肿瘤中的意义，以及癌症特异性蛋白质异构体对于下一代癌症治疗和诊断的关键作用。
技术的最新进展使人们对肿瘤发生的潜在机制有了更好的理解。这对于开发更有效和危害更小的治疗方法至关重要，这些方法基于直接靶向改变的蛋白质和失调的途径。随着蛋白质组覆盖范围和检测复杂蛋白质异构体的能力的提高，最需要改变的是数据汇编和数据库可用性，以进行高级数据分析，并允许更好地对蛋白质异构体进行功能注释。
