Department of Pathology, University of Washington School of Medicine MB 357705, 1959 NE Pacific St., Seattle, WA 98195, United States.
Semin Cancer Biol. 2010 Oct;20(5):294-303. doi: 10.1016/j.semcancer.2010.10.008. Epub 2010 Oct 15.
Cancer arises as the result of a natural selection process among cells of the body, favoring lineages bearing somatic mutations that bestow them with a proliferative advantage. Of the thousands of mutations within a tumor, only a small fraction functionally drive its growth; the vast majority are mere passengers of minimal biological consequence. Yet the presence of any mutation, independent of its role in facilitating proliferation, tags a cell's clonal descendants in a manner that allows them to be distinguished from unrelated cells. Such markers of cell lineage can be used to identify the abnormal proliferative signature of neoplastic clonal evolution, even at a stage which predates morphologically recognizable dysplasia. This article focuses on molecular techniques for assessing cellular clonality in humans with an emphasis on how they may be used for early detection of tumorigenic processes. We discuss historical as well as contemporary approaches and consider ways in which powerful new genomic technologies might be harnessed to develop a future generation of early cancer diagnostics.
癌症是机体细胞自然选择的结果，有利于携带赋予其增殖优势的体细胞突变的谱系。在肿瘤内的数千个突变中，只有一小部分能够有效地驱动其生长；绝大多数只是具有最小生物学意义的乘客。然而，任何突变的存在，无论其在促进增殖中的作用如何，都会以一种能够将其与无关细胞区分开来的方式标记细胞的克隆后代。这种细胞谱系的标记物可用于鉴定肿瘤克隆进化的异常增殖特征，甚至在形态上可识别的发育不良之前就可以检测到。本文重点介绍用于评估人类细胞克隆性的分子技术，重点介绍如何将其用于早期检测肿瘤发生过程。我们讨论了历史和当代的方法，并考虑了如何利用强大的新基因组技术来开发新一代早期癌症诊断方法。
