人口动态是癌症的驱动因素。

IF 3.3 3区 医学 Q2 ONCOLOGY
Mariana Dos Santos Oliveira, Marcelo de C Griebeler, Bernardo Henz, Filipe Ferreira Dos Santos, Gabriela D A Guardia, Helena B Conceição, Pedro A F Galante, Darlan C Minussi, Manuel M Oliveira, Guido Lenz
{"title":"人口动态是癌症的驱动因素。","authors":"Mariana Dos Santos Oliveira, Marcelo de C Griebeler, Bernardo Henz, Filipe Ferreira Dos Santos, Gabriela D A Guardia, Helena B Conceição, Pedro A F Galante, Darlan C Minussi, Manuel M Oliveira, Guido Lenz","doi":"10.1093/carcin/bgae038","DOIUrl":null,"url":null,"abstract":"<p><p>Most tissues are continuously renovated through the division of stem cells and the death of old or damaged cells, which is known as cell turnover rate (CTOR). Despite being in steady state, tissues have different population dynamics and leading to diverse clonality levels. Here, we propose and test that cell population dynamics can be a cancer driver. We employed the evolutionary software esiCancer to show that CTOR, within a range comparable to what is observed in human tissues, can amplify the risk of a mutation due to ancestral selection (ANSEL). In a high CTOR tissue, a mutated ancestral cell is likely to be selected and persist over generations, which leads to a scenario of elevated ANSEL profile, characterized by few niches of large clones, which does not occur in low CTOR. We found that CTOR is significantly associated with the risk of developing cancer, even when correcting for mutation load, indicating that population dynamics per se is a cancer driver. This concept is central to understanding cancer risk and for the design of new therapeutic interventions that minimize the contribution of ANSEL in cancer growth.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Population Dynamics is a Cancer Driver.\",\"authors\":\"Mariana Dos Santos Oliveira, Marcelo de C Griebeler, Bernardo Henz, Filipe Ferreira Dos Santos, Gabriela D A Guardia, Helena B Conceição, Pedro A F Galante, Darlan C Minussi, Manuel M Oliveira, Guido Lenz\",\"doi\":\"10.1093/carcin/bgae038\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Most tissues are continuously renovated through the division of stem cells and the death of old or damaged cells, which is known as cell turnover rate (CTOR). Despite being in steady state, tissues have different population dynamics and leading to diverse clonality levels. Here, we propose and test that cell population dynamics can be a cancer driver. We employed the evolutionary software esiCancer to show that CTOR, within a range comparable to what is observed in human tissues, can amplify the risk of a mutation due to ancestral selection (ANSEL). In a high CTOR tissue, a mutated ancestral cell is likely to be selected and persist over generations, which leads to a scenario of elevated ANSEL profile, characterized by few niches of large clones, which does not occur in low CTOR. We found that CTOR is significantly associated with the risk of developing cancer, even when correcting for mutation load, indicating that population dynamics per se is a cancer driver. This concept is central to understanding cancer risk and for the design of new therapeutic interventions that minimize the contribution of ANSEL in cancer growth.</p>\",\"PeriodicalId\":9446,\"journal\":{\"name\":\"Carcinogenesis\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-06-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Carcinogenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/carcin/bgae038\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Carcinogenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/carcin/bgae038","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

大多数组织通过干细胞的分裂和老化或受损细胞的死亡不断更新,这被称为细胞更替率(CTOR)。尽管组织处于稳定状态,但它们的细胞群动态各不相同,导致克隆水平各异。在此,我们提出并验证了细胞群动态可能是癌症驱动因素。我们利用进化软件 esiCancer 显示,在与人体组织中观察到的情况相当的范围内,CTOR 可以放大由于祖先选择(ANSEL)而导致的突变风险。在高 CTOR 组织中,突变的祖先细胞很可能会被选择并持续数代,从而导致 ANSEL 曲线升高,其特点是大克隆的壁龛很少,而在低 CTOR 组织中不会出现这种情况。我们发现,即使校正了突变负荷,CTOR 仍与患癌风险显著相关,这表明种群动态本身就是癌症的驱动因素。这一概念对于理解癌症风险和设计新的治疗干预措施(最大限度地减少 ANSEL 在癌症生长中的作用)至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Population Dynamics is a Cancer Driver.

Most tissues are continuously renovated through the division of stem cells and the death of old or damaged cells, which is known as cell turnover rate (CTOR). Despite being in steady state, tissues have different population dynamics and leading to diverse clonality levels. Here, we propose and test that cell population dynamics can be a cancer driver. We employed the evolutionary software esiCancer to show that CTOR, within a range comparable to what is observed in human tissues, can amplify the risk of a mutation due to ancestral selection (ANSEL). In a high CTOR tissue, a mutated ancestral cell is likely to be selected and persist over generations, which leads to a scenario of elevated ANSEL profile, characterized by few niches of large clones, which does not occur in low CTOR. We found that CTOR is significantly associated with the risk of developing cancer, even when correcting for mutation load, indicating that population dynamics per se is a cancer driver. This concept is central to understanding cancer risk and for the design of new therapeutic interventions that minimize the contribution of ANSEL in cancer growth.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信