Oncogenetic tree model of somatic mutations and DNA methylation in colon tumors.
Oncogenetic tree model of somatic mutations and DNA methylation in colon tumors.
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DOI：
10.1002/gcc.20614
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发表时间：
2009-01
影响因子：
3.7
通讯作者：
Slattery, Martha L.
中科院分区：
文献类型：
--
作者：
Sweeney, Carol;Boucher, Kenneth M.;Samowitz, Wade S.;Wolff, Roger K.;Albertsen, Hans;Curtin, Karen;Caan, Bette J.;Slattery, Martha L.
我们对结肠癌中体细胞改变的理解已经从一系列事件发生在单个序列中的概念发展到对多个途径的认识。肿瘤发生树是一种模型，旨在描述致癌过程中体细胞改变的途径和顺序，而不假设肿瘤将属于相互排斥的类别。我们将该模型应用于结肠肿瘤体细胞改变的数据。使用TP53、KRAS 2、APC和BRAF基因突变、MLH 1和p16基因CpG位点甲基化、肿瘤标记物甲基化（MINT）和微卫星不稳定性（MSI）数据，构建了一个肿瘤遗传树模型，该模型来自一个基于人群的系列，共971例结肠肿瘤。肿瘤发生树分析产生具有三个分支的可再现树。该模型将MINT标志物的甲基化表示为启动分支并倾向于MSI、MHL 1和p16的甲基化以及BRAF突变。APC突变是独立分支中的第一个突变，随后是TP 53突变。KRAS 2突变被置于第三个独立的分支，这意味着它既不依赖于其他改变，也不倾向于其他改变。观察到个体肿瘤具有代表一个、两个或所有三个分支的每种组合的改变模式。肿瘤发生树模型的假设是适当的观察到的异质性结肠肿瘤，该模型产生了一个有用的视觉示意图的序列中的事件的结肠癌发生的途径。
Our understanding of somatic alterations in colon cancer has evolved from a concept of a series of events taking place in a single sequence to a recognition of multiple pathways. An oncogenetic tree is a model intended to describe the pathways and sequence of somatic alterations in carcinogenesis without assuming that tumors will fall in mutually exclusive categories. We applied this model to data on colon tumor somatic alterations. An oncogenetic tree model was built using data on mutations of TP53, KRAS2, APC, and BRAF genes, methylation at CpG sites of MLH1 and p16 genes, methylation in tumor (MINT) markers, and microsatellite instability (MSI) for 971 colon tumors from a population-based series. Oncogenetic tree analysis resulted in a reproducible tree with three branches. The model represents methylation of MINT markers as initiating a branch and predisposing to MSI, methylation of MHL1 and p16, and BRAF mutation. APC mutation is the first alteration in an independent branch and is followed by TP53 mutation. KRAS2 mutation was placed a third independent branch, implying that it neither depends on, nor predisposes to, the other alterations. Individual tumors were observed to have alteration patterns representing every combination of one, two, or all three branches. The oncogenetic tree model assumptions are appropriate for the observed heterogeneity of colon tumors, and the model produces a useful visual schematic of the sequence of events in pathways of colon carcinogenesis.
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影响因子：
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作者：
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