年龄将癌症基因组中的选择与因果区分开来
年龄将癌症基因组中的选择与因果区分开来
作者： 小柯机器人 发布时间：2026/5/6 15:40:02
本期文章：《自然—遗传学》：Online/在线发表
2026年5月5日出版的《自然—遗传学》杂志发表了美国科学家的一项最新研究成果。来自哈佛医学院的Kamila Naxerova团队研制了年龄将癌症基因组中的选择与因果区分开来。
在这里，该团队发展了一个统计框架来解开正常组织中的选择和癌变的诱导。通过比较癌症和正常组织基因组，小组估计了突变对血液、食管和结肠中癌症风险的影响。该研究团队确定较强的癌症导管突变在较年轻的患者中富集。这使得即使没有正常组织数据，也可以从患者的年龄分布中识别出癌症导管突变。
此外，该课题组人员发现急性髓系白血病的年龄依赖性可以通过正常的血液进化来解释，这挑战了长期以来儿童癌症需要不同突变的观点。总的来说，他们的框架描述了正常组织衰老的致癌作用，改善了突变所带来的癌症风险的评估。
据了解，癌症导管突变主要是从癌症基因组中的正选择信号中确定的。然而，正选择也是正常组织衰老的普遍特征。
附：英文原文
Title: Age distinguishes selection from causation in cancer genomes
Author: Cheek, David, Blohmer, Martin, Nowak, Martin A., Antal, Tibor, Naxerova, Kamila
Issue&Volume: 2026-05-05
Abstract: Cancer-causing mutations have been identified primarily from positive selection signals in cancer genomes. However, positive selection is also a ubiquitous feature of normal tissue aging. Here we develop a statistical framework to disentangle selection in normal tissue and causation of carcinogenesis. By comparing cancer and normal tissue genomes, we estimate the effects of mutations on cancer risk in the blood, esophagus and colon. We determine that stronger cancer-causing mutations are enriched at younger patient ages. This enables cancer-causing mutations to be identified from patient age distributions, even without normal tissue data. Moreover, we show for acute myeloid leukemia that the age-dependence of purported causal mutations can be explained largely by normal blood evolution, challenging the long-standing notion that childhood cancers require distinct mutations. Broadly, our framework delineates carcinogenesis from normal tissue aging, improving the assessment of cancer risk conferred by mutations.
DOI: 10.1038/s41588-026-02593-z
Source: https://www.nature.com/articles/s41588-026-02593-z