文章：

非癌组织中克隆扩增

Clonal expansion in non-cancer tissues

原文发布日期：2021-02-24

DOI: 10.1038/s41568-021-00335-3

类型: Review Article

开放获取: 否

英文摘要：

Cancer is a clonal disorder derived from a single ancestor cell and its progenies that are positively selected by acquisition of ‘driver mutations’. However, the evolution of positively selected clones does not necessarily imply the presence of cancer. On the contrary, it has become clear that expansion of these clones in phenotypically normal or non-cancer tissues is commonly seen in association with ageing and/or in response to environmental insults and chronic inflammation. Recent studies have reported expansion of clones harbouring mutations in cancer driver genes in the blood, skin, oesophagus, bronchus, liver, endometrium and bladder, where the expansion could be so extensive that tissues undergo remodelling of an almost entire tissue. The presence of common cancer driver mutations in normal tissues suggests a strong link to cancer development, providing an opportunity to understand early carcinogenic processes. Nevertheless, some driver mutations are unique to normal tissues or have a mutation frequency that is much higher in normal tissue than in cancer, indicating that the respective clones may not necessarily be destined for evolution to cancer but even negatively selected for carcinogenesis depending on the mutated gene. Moreover, tissues that are remodelled by genetically altered clones might define functionalities of aged tissues or modified inflammatory processes. In this Review, we provide an overview of major findings on clonal expansion in phenotypically normal or non-cancer tissues and discuss their biological significance not only in cancer development but also in ageing and inflammatory diseases.

摘要翻译： 

癌症是一种克隆性疾病，源自单一祖细胞及其后代，这些细胞通过获得“驱动突变”而被正向选择。然而，正向选择克隆的演化并不必然意味着癌症的存在。相反，研究表明这些克隆在表型正常或非癌组织中的扩增常与衰老和/或环境损伤及慢性炎症相关。近期研究报道了在血液、皮肤、食管、支气管、肝脏、子宫内膜和膀胱中存在携带癌症驱动基因突变的克隆扩增，这种扩增可能极为广泛，导致几乎整个组织发生重塑。正常组织中常见癌症驱动突变的存在提示其与癌症发展密切相关，为了解早期致癌过程提供了契机。然而，某些驱动突变仅存在于正常组织中，或其突变频率远高于癌症组织，表明相应克隆未必注定会演化为癌症，甚至可能因突变基因的不同而在致癌过程中被负向选择。此外，经遗传改变克隆重塑的组织可能定义了衰老组织的功能或修饰了炎症过程。本综述将概述表型正常或非癌组织中克隆扩增的重要发现，并探讨其在癌症发展、衰老及炎症性疾病中的生物学意义。

原文链接：

Clonal expansion in non-cancer tissues