From Colitis to Cancer: An Evolutionary Trajectory That Merges Maths and Biology.
From Colitis to Cancer: An Evolutionary Trajectory That Merges Maths and Biology.
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DOI：
10.3389/fimmu.2018.02368
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发表时间：
2018
影响因子：
7.3
通讯作者：
Graham TA
中科院分区：
文献类型：
--
作者：
Al Bakir I;Curtius K;Graham TA
炎症性肠病患者发生结直肠癌的风险增加，这种风险与疾病持续时间，程度和累积炎症负担有关。癌变遵循达尔文进化的原则，体细胞获得基因组改变，为它们提供生存和/或生长优势。结肠炎代表了一种独特的情况，常规监测内窥镜检查提供了一个偶然的机会，观察人体器官体内随时间和空间的躯体演变。此外，结肠炎的体细胞进化是在“快车道”上的进化：疾病特征的反复炎症和粘膜愈合加速了进化过程，并可能为炎症适应表型性状提供了强大的选择压力。在这篇综述中，我们讨论了结肠炎中肿瘤前克隆的进化动力学，重点是如何测量它们的进化轨迹，从而提供一种预测未来癌症发生的有力方法。体细胞进化的测量需要一个跨学科的方法，结合定量测量的基因型，表型和体细胞的微环境，特别注意跨结肠的空间异质性，连同数学建模来解释这些数据在一个进化的框架。在这里，我们采取了一种实用的方法来讨论如何以及为什么不同的“进化成分”可以和应该被测量，以及我们对随后转化为临床实践的观点。我们强调了结肠炎相关癌症演变中的开放性问题，作为对未来工作的刺激。
Patients with inflammatory bowel disease have an increased risk of developing colorectal cancer, and this risk is related to disease duration, extent, and cumulative inflammation burden. Carcinogenesis follows the principles of Darwinian evolution, whereby somatic cells acquire genomic alterations that provide them with a survival and/or growth advantage. Colitis represents a unique situation whereby routine surveillance endoscopy provides a serendipitous opportunity to observe somatic evolution over space and time in vivo in a human organ. Moreover, somatic evolution in colitis is evolution in the ‘fast lane': the repeated rounds of inflammation and mucosal healing that are characteristic of the disease accelerate the evolutionary process and likely provide a strong selective pressure for inflammation-adapted phenotypic traits. In this review, we discuss the evolutionary dynamics of pre-neoplastic clones in colitis with a focus on how measuring their evolutionary trajectories could deliver a powerful way to predict future cancer occurrence. Measurements of somatic evolution require an interdisciplinary approach that combines quantitative measurement of the genotype, phenotype and the microenvironment of somatic cells–paying particular attention to spatial heterogeneity across the colon–together with mathematical modeling to interpret these data within an evolutionary framework. Here we take a practical approach in discussing how and why the different “evolutionary ingredients” can and should be measured, together with our viewpoint on subsequent translation into clinical practice. We highlight the open questions in the evolution of colitis-associated cancer as a stimulus for future work.
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影响因子：
16.6
作者：
Arthur, Janelle C.;Gharaibeh, Raad Z.;Muehlbauer, Marcus;Perez-Chanona, Ernesto;Uronis, Joshua M.;McCafferty, Jonathan;Fodor, Anthony A.;Jobin, Christian
通讯作者：
Jobin, Christian
影响因子：
24.5
作者：
Baker AM;Cross W;Curtius K;Al Bakir I;Choi CR;Davis HL;Temko D;Biswas S;Martinez P;Williams MJ;Lindsay JO;Feakins R;Vega R;Hayes SJ;Tomlinson IPM;McDonald SAC;Moorghen M;Silver A;East JE;Wright NA;Wang LM;Rodriguez-Justo M;Jansen M;Hart AL;Leedham SJ;Graham TA
通讯作者：
Graham TA
影响因子：
24.5
作者：
Choi CR;Al Bakir I;Ding NJ;Lee GH;Askari A;Warusavitarne J;Moorghen M;Humphries A;Ignjatovic-Wilson A;Thomas-Gibson S;Saunders BP;Rutter MD;Graham TA;Hart AL
通讯作者：
Hart AL
影响因子：
3.6
作者：
Bjerrum, Jacob Tveiten;Wang, Yulan;Hao, Fuhua;Coskun, Mehmet;Ludwig, Christian;Guenther, Ulrich;Nielsen, Ole Haagen
通讯作者：
Nielsen, Ole Haagen
染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC