The critical roles of somatic mutations and environmental tumor-promoting agents in cancer risk.
The critical roles of somatic mutations and environmental tumor-promoting agents in cancer risk.
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DOI：
10.1038/s41588-020-00727-5
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发表时间：
2020-11
期刊：
影响因子：
30.8
通讯作者：
Balmain A
中科院分区：
文献类型：
--
作者：
Balmain A
癌症是由“癌症驱动”基因的基因组突变驱动的，这些基因在肿瘤发展中起着关键作用。这些突变可能是由环境中诱变剂的暴露或组织干细胞内源性DNA复制错误引起的。最近对组织学正常的人体组织中大量突变（包括癌症驱动突变）的观察表明，仅突变不足以导致肿瘤发展，从而引发了单个突变细胞如何引发肿瘤形成的问题。在一个有来自小鼠肿瘤模型的数十年数据支持的概念中，非诱变的肿瘤促进剂被假定可激活休眠突变细胞的增殖，从而产生活跃生长的病变，其中促进阶段是肿瘤形成的限速步骤。因此，内源性或环境性的非诱变促进剂在人类癌症病因学中可能比以前认为的具有更重要的作用。
Cancer is driven by genomic mutations in ‘cancer driver’ genes, which have essential roles in tumor development. These mutations may be caused by exposure to mutagens in the environment or by endogenous DNA-replication errors in tissue stem cells. Recent observations of abundant mutations, including cancer driver mutations, in histologically normal human tissues suggest that mutations alone are not sufficient for tumor development, thus prompting the question of how single mutant cells give rise to neoplasia. In a concept supported by decades-old data from mouse tumor models, non-mutagenic tumor-promoting agents have been posited to activate the proliferation of dormant mutated cells, thus generating actively growing lesions, with the promotion stage as the rate-limiting step in tumor formation. Non-mutagenic promoting agents, either endogenous or environmental, may therefore have a more important role in human cancer etiology than previously thought.
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DOI：
10.1126/science.aau3879
发表时间：
2018-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Martincorena I;Fowler JC;Wabik A;Lawson ARJ;Abascal F;Hall MWJ;Cagan A;Murai K;Mahbubani K;Stratton MR;Fitzgerald RC;Handford PA;Campbell PJ;Saeb-Parsy K;Jones PH
通讯作者：
Jones PH
影响因子：
3.6
作者：
GOERTTLER, K;LOEHRKE, H;HESSE, B
通讯作者：
HESSE, B
影响因子：
64.8
作者：
Moore, Luiza;Leongamornlert, Daniel;Stratton, Michael R.
通讯作者：
Stratton, Michael R.
影响因子：
64.8
作者：
Lee-Six, Henry;Olafsson, Sigurgeir;Stratton, Michael R.
通讯作者：
Stratton, Michael R.
影响因子：
8.8
作者：
BERENBLUM, I;SHUBIK, P
通讯作者：
SHUBIK, P