Why precursors matter.
Why precursors matter.
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DOI：
10.1158/1055-9965.epi-13-0135
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Caporaso NE
中科院分区：
文献类型：
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作者：
Caporaso NE
癌症前体是癌症的组织前因。它们与生物标志物的区别在于它们反映了与特定癌症的形态学而不仅仅是生物化学或遗传关联。癌症前体越来越被认为是普遍存在的，与致癌作用有关，并为初级和二级预防提供了独特的潜力。随着研究它们的分子、成像和基因组工具的发展，越来越明显的是，几乎所有的恶性肿瘤都是在这些临床沉默状态之前出现的，其中出现了表征特定癌症的分子病变。从时间和先行分子事件来看，癌症是可见的冰山;淹没的90%是前兆。我们还认为，所有形态学变化都必须伴随着广泛的和近端的分子改变。在生物学上，分子和形态学病变必须对应，但我们对它们之间关系的理解仍然有限。Vogelstein关于结肠癌进展的分子步骤的经典范例（1）和其他肿瘤的类似模式仍然不完整。本综述的一个关键主题是，理解肿瘤分子分类学以及决定其进展（前体>肿瘤>转移）的最直接途径应该强调在人群研究中研究前体病变（图1）。在这里，详细信息的暴露和结果结合生物标志物研究新技术和迅速扩大的肿瘤分子和基因组病变数据库有望揭示恶性肿瘤的基础，并带来以下益处：对病因学的新认识，筛查和预防的重新振兴，以及增强治疗设备的潜力。大规模的先进技术计划，如肿瘤癌症基因组图谱（TCGA）专注于肿瘤组织表征和基因组功能元件的ENCODE（2）。这些努力和其他旨在阐明肿瘤形成的体细胞基础（以及动态基因组的表达、甲基化和其他表现）的努力，
Cancer precursors are the tissue antecedents of cancer. They are distinguished from biomarkers in that they reflect a morphologic as opposed to a merely biochemical or genetic association with a specific cancer. Precursors to cancers are increasingly recognized as universal, relevant to carcinogenesis, and providing a unique potential for primary and secondary prevention. As the molecular, imaging, and genomic tools to investigate them evolve, it is becoming increasingly evident that virtually all malignancies are preceded by these clinically silent states where the molecular lesions that characterize the specific cancer emerge. In terms of both time and antecedent molecular events, cancer is the visible iceberg; the 90% submerged is the precursor. We also take it as axiomatic that all morphologic changes must be accompanied by an extensive and proximal scaffolding of molecular alterations. Biologically, molecular and morphologic lesions must correspond, but our understanding of their relationship is still limited. Vogelstein’s classic paradigm (1) for the molecular steps in progression to colon cancer and similar schemas for other tumors remain incomplete. A key theme of this review is that the most direct path to understanding the molecular taxonomy of tumors and what determines their progression (precursor> tumor> metastasis) should emphasize investigating precursor lesions in population studies (Fig. 1). Here, detailed information on exposure and outcome combined with biomarker studies (serial where possible) can characterize molecular steps in progression and refine their relation to morphology.New technologies and the rapidly expanding database of molecular and genomic lesions in tumors are expected to reveal the underpinnings of malignancy with attendant benefits: new insight into etiology, reinvigoration of screening and prevention, and potential to enhance the therapeutic armamentarium. Large-scale advanced technology initiatives such as the Tumor Cancer Genome Atlas (TCGA) focuses on tumor tissue characterization and ENCODE on functional elements of the genome (2). These efforts and others that aim to elucidate the somatic underpinnings (as well as expression, methylation, and other manifestations of a dynamic genome) of neoplasia