Cancer-associated mutations in healthy individuals: assessing the risk of carcinogenesis.
Cancer-associated mutations in healthy individuals: assessing the risk of carcinogenesis.
复制标题
健康个体中与癌症相关的突变：评估致癌风险。
DOI：
10.1158/0008-5472.can-13-1452
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发表时间：
2014
期刊：
影响因子：
11.2
通讯作者：
Wodarz,Dominik
中科院分区：
文献类型：
--
作者：
Rodriguez-Brenes,IgnacioA;Komarova,NataliaL;Wodarz,Dominik
与造血系统恶性肿瘤相关的突变已在健康个体中反复鉴定。对于某些情况，如t（14;18）易位和单克隆B细胞淋巴细胞增多症，异常细胞的存在与后来的癌症发展之间没有明确的联系。有趣的是，纵向研究表明，这些异常在一些个体中持续很长一段时间，但在另一些个体中是短暂的，它们完全消失。在这里，我们提出了一个数学模型，基于细胞复制限制，为这些看似矛盾的发现提供了一个可能的解释。它提出，表型的短暂和持久的性质取决于突变起源的给定谱系的分化途径中的阶段。我们的工作表明，细胞复制限制不仅可以通过中止细胞的克隆扩增来预防癌症，而且可以通过影响健康组织中改变但非肿瘤细胞的命运来预防癌症。©2014 AACR.
Mutations associated with hematopoietic malignancies have been repeatedly identified in healthy individuals. For certain cases, such as the t(14;18) translocation and monoclonal B-cell lymphocytosis, no clear link between the presence of aberrant cells and the later development of cancer has been established. Intriguingly, longitudinal studies suggest that these abnormalities persist for long periods of time in some individuals, but in others are transient in which they disappear completely. Here, we present a mathematical model, based on cellular replication limits, that provides a possible explanation for these seemingly contradictory findings. It proposes that the transient and persistent nature of the phenotypes depends on the stage in the differentiation pathway of a given lineage in which the mutation originates. Our work suggests that cellular replication limits may not only prevent cancer by aborting clonal expansion of cells, but also by influencing the fate of altered but nonneoplastic cells in healthy tissue.Cancer Res; 74(6); 1661–9. ©2014 AACR.