文章：

场域癌变的进化观点

An evolutionary perspective on field cancerization

原文发布日期：2017-12-08

DOI: 10.1038/nrc.2017.102

类型: Review Article

开放获取: 否

要点：

1. Mutations naturally accrue and clonally expand in ageing tissues, but only a subset of these mutations increases the risk of cancer development.
2. A cancerized lineage is one that has acquired some but not all the phenotypic traits required for malignancy. Typically, this means that a cancerized lineage has a survival or growth advantage over normal cells but is incapable of growing into a tumour.
3. Field cancerization is both enabled by and causes changes to the tissue microenvironment.
4. Mutagen exposure and naturally occurring age-related mutations initiate cancerized fields.
5. Field cancerization can occur without morphological change, meaning that histopathology of a tissue alone is an inadequate biomarker of cancer risk.
6. Measurements of the evolution of the cancerized field offer promise as a new class of biomarker of cancer risk and provide a means to mechanistically assess the impact of chemoprevention strategies.
7. Longitudinally collected tissue samples from patients undergoing surveillance in tissues frequently affected by field cancerization provide an underexploited resource for the study of clonal evolution over space and time in humans.

要点翻译：

1. 突变在衰老的组织中自然累积并克隆性扩张，但其中只有一部分突变会增加癌症发生的风险。
2. 癌化谱系是指获得了恶性肿瘤所需的部分但非全部表型特征的细胞系。通常，这意味着癌化谱系相较于正常细胞具有生存或生长优势，但无法发展成肿瘤。
3. 区域癌化既由组织微环境的改变促成，同时也引起微环境的改变。
4. 诱变剂暴露和自然发生的年龄相关突变会启动癌化区域。
5. 区域癌化可在不伴随形态学变化的情况下发生，这意味着仅凭组织的病理学检查不足以作为癌症风险的生物标志物。
6. 对癌化区域演变的测量有望成为一类新型的癌症风险生物标志物，并为从机制上评估化学预防策略的效果提供方法。
7. 在常受区域癌化影响的组织中，接受监测的患者纵向采集的组织样本为研究人类克隆演化在空间和时间上的变化提供了尚未被充分开发的资源。

英文摘要：

Tumorigenesis begins long before the growth of a clinically detectable lesion and, indeed, even before any of the usual morphological correlates of pre-malignancy are recognizable. Field cancerization, which is the replacement of the normal cell population by a cancer-primed cell population that may show no morphological change, is now recognized to underlie the development of many types of cancer, including the common carcinomas of the lung, colon, skin, prostate and bladder. Field cancerization is the consequence of the evolution of somatic cells in the body that results in cells that carry some but not all phenotypes required for malignancy. Here, we review the evidence of field cancerization across organs and examine the biological mechanisms that drive the evolutionary process that results in field creation. We discuss the clinical implications, principally, how measurements of the cancerized field could improve cancer risk prediction in patients with pre-malignant disease.

摘要翻译： 

肿瘤的发生远早于临床上可检测到的病变出现之前，甚至早于任何可识别的癌前形态学改变。所谓“区域癌化”（field cancerization），是指正常细胞群体被已具备癌变潜能但可能无形态学改变的细胞群体所取代的现象，目前已被认为是多种癌症（包括肺、结肠、皮肤、前列腺和膀胱等常见癌种）发生的基础。区域癌化是体内体细胞演化的结果，这些细胞虽获得了部分恶性表型，但尚未具备全部恶性特征。本文综述了不同器官中区域癌化的证据，并探讨了驱动区域形成的演化过程的生物学机制；同时讨论了其临床意义，主要在于如何通过检测癌化区域来提高对癌前病变患者的癌症风险预测能力。

原文链接：

An evolutionary perspective on field cancerization