National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
Cancer Biomark. 2010;9(1-6):41-64. doi: 10.3233/CBM-2011-0204.
It has become increasingly evident that the study of DNA is inadequate to explain many, if not most, aspects of the development and progression of neoplastic lesions from pre-invasive lesions to metastasis. Thus, the term "genetic" can no longer refer to just the study of the genome. Much of the action in genetic research now shifts to the methods by which the pre-mRNA from one gene is processed to yield multiple different proteins, different quantities of the same protein as well as other forms of regulating RNA. Thus, the age of post-transcriptional processing and epigenetic control of the transfer of information from the genome has arrived. The mechanisms of post-transcriptional processing and epigenetic control that must be characterized in greater detail including alternate splicing, regulation of mRNA degradation, RNA regulatory factors including those factors which extensively edit mRNAs, control of translation, and control of protein stability and degradation. This chapter reviews many of the processes that control information from the genome to proteins and how these factors lead from less than 40,000 genes to more than an order of magnitude increase more proteins which actually control the phenotypes of cells - normal or neoplastic. It is usually the products of genes (e.g., mRNA, microRNA and proteins) that are the molecular markers that will control translational research and ultimately, individualized (personal) medical approaches to disease. This chapter emphasizes how the process of neoplasia "hijacks" the normal processes of cellular operations, especially those processes that are important in the normal development of the organisms - including proliferation, cellular death, angiogenesis, cellular mobility and invasion, and immunoregulation to ensure neoplastic development, survival and progression. This chapter reviews the wide range of processes controlling the information that flows from the genome to proteins and emphasizes how molecular steps in pure processes can be used as biomarkers to study prevention, treatment and/or management of diseases.
越来越明显的是，研究 DNA 不足以解释许多（如果不是大多数）肿瘤病变从早期病变到转移的发展和进展的方面。因此，“遗传”一词不能再仅仅指基因组的研究。现在，遗传研究的大部分工作都转移到了研究从一个基因产生多个不同蛋白质的前 mRNA 的方法上，研究同一种蛋白质的不同数量以及其他形式的调节 RNA。因此，从基因组中转录后处理和表观遗传控制信息传递的时代已经到来。必须更详细地描述转录后处理和表观遗传控制的机制，包括可变剪接、mRNA 降解的调节、RNA 调节因子（包括那些广泛编辑 mRNAs 的因子）、翻译的控制以及蛋白质稳定性和降解的控制。本章回顾了许多控制从基因组到蛋白质的信息的过程，以及这些因素如何从不到 40000 个基因增加到超过一个数量级的更多蛋白质，而这些蛋白质实际上控制着细胞的表型——正常或肿瘤。通常是基因的产物（例如 mRNA、microRNA 和蛋白质）作为分子标记，控制着转化研究，最终控制着针对疾病的个体化（个人化）医疗方法。本章强调了肿瘤发生过程如何“劫持”细胞操作的正常过程，特别是那些在生物正常发育中很重要的过程，包括增殖、细胞死亡、血管生成、细胞迁移和侵袭以及免疫调节，以确保肿瘤的发展、生存和进展。本章回顾了控制从基因组到蛋白质的信息的广泛过程，并强调了纯过程中的分子步骤如何可以用作生物标志物来研究疾病的预防、治疗和/或管理。
