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小豪读文献 癌症组织中癌细胞由于携带基因突变的不同，因此具有较高的异质性。研究发现，随着年龄的增长、细胞的不断增值，人类基因会不断地积累各种突变，人体通过对突变细胞和基因进行一定的选择，在某些状况下，具有癌症驱动性的基因突变会被保留下来，最终导致癌症发生。但是，在癌症发生之前，具有癌症驱动基因的细胞往往会以正常细胞的形态存在。那么究竟是什么因素导致了人类从婴儿到老年时期发生基因突变、以及如何筛选癌症驱动基因——这些问题仍困扰着我们。近期国际著名学术期刊《Nature》上发表的一篇文章，系统的揭示了不良生活习惯会加快人体对具有癌症驱动基因细胞的筛选，并加快这些细胞的增殖，进而增加癌症发生的风险。因此，尽早戒烟，合理饮酒，养成良好的生活习惯对于人类的健康是十分必要的。 Age-related remodelling of oesophageal epithelia by mutated cancer drivers 图片来源：文献原文 Clonal expansion in aged normal tissues has been implicated in the development of cancer. However, the chronology and risk dependence of the expansion are poorly understood. Here we intensively sequence 682 micro-scale oesophageal samples and show, in physiologically normal oesophageal epithelia, the progressive age-related expansion of clones that carry mutations in driver genes (predominantly NOTCH1), which is substantially accelerated by alcohol consumption and by smoking. Driver-mutated clones emerge multifocally from early childhood and increase their number and size with ageing, and ultimately replace almost the entire oesophageal epithelium in the extremely elderly. Compared with mutations in oesophageal cancer, there is a marked overrepresentation of NOTCH1 and PPM1D mutations in physiologically normal oesophageal epithelia; these mutations can be acquired before late adolescence (as early as early infancy) and significantly increase in number with heavy smoking and drinking. The remodelling of the oesophageal epithelium by driver-mutated clones is an inevitable consequence of normal ageing, which—depending on lifestyle risks—may affect cancer development. 癌种突变驱动因子导致年龄相关的食管上皮细胞重构 随着年龄增大，在衰老的组织中，细胞的克隆增殖与癌症发展有关。但是，人们对于这种衰老与风险之间的联系研究还不够深入。研究人员通过对682例患者的食管样品测序发现，携带NOTCH1癌症驱动基因突变的人群，随着年龄的增长，饮酒和吸烟的生活习惯会导致细胞克隆分裂的速度大大提高。驱动基因的突变从较早的儿童时期便开始出现，随着年龄的增加数目也会随之增加，最终这些具有突变的食管上皮细胞会完全取代之前的正常细胞。通过对食管上皮细胞测序数据进行对比发现，具有癌症驱动基因 NOTCH1和PPM1D突变的细胞最早会出现在青春期之后，甚至于婴儿时期。当成年之后，具有这些突变的人群如果酗酒或重度抽烟的话，这些具有癌症驱动基因的细胞的增殖速度将大大加快。这种不良生活习惯随着年龄的增长，携带癌症驱动基因的细胞也大大增加，最终增加患癌风险。 文献来源 Yokoyama, A. et al. (2018). Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature, 565. Doi:10.1038/s41586-018-0811-x 备注：浦美医学每周推出一个专题的“文献速递”汇编，如需详细了解内容或全文请联系我们（浦美小编：微信号pumeixiaobian）。文献内容均由浦美医学编译自原文，疏漏之处敬请读者指正。 |
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