A computational model incorporating neural stem cell dynamics reproduces glioma incidence across the lifespan in the human population.
A computational model incorporating neural stem cell dynamics reproduces glioma incidence across the lifespan in the human population.
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DOI：
10.1371/journal.pone.0111219
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Stoll E
中科院分区：
文献类型：
--
作者：
Bauer R;Kaiser M;Stoll E
神经胶质瘤是原发性脑肿瘤最常见的形式。从人口统计学角度来看，直到老年，发生这种情况的风险都会增加。在这里，我们提出了一种新颖的计算模型来重现整个生命周期中神经胶质瘤的发病概率。先前解释神经胶质瘤发病率的数学模型是以相当抽象的方式构建的，并且与实证结果没有直接关系。为了缩小理论和实验观察之间的差距，我们整合了有关神经胶质瘤发生的细胞和分子因素的最新数据。由于证据表明成体神经干细胞可能是神经胶质瘤的起源细胞，因此我们将根据经验确定的神经干细胞数量、细胞分裂率、突变率和致癌潜力的估计值纳入我们的模型中。我们证明我们的模型产生的结果与人口中的实际人口统计数据相匹配。特别是，该模型解释了观察到的神经胶质瘤发病高峰在大约 80 岁，无需断言整个人群的易感性存在差异。总体而言，我们的模型支持神经胶质瘤是由神经干细胞群内随机发生的致癌突变引起的假设。基于该模型，我们评估了衰老过程中（实验表明）神经干细胞数量减少和细胞分裂率增加的影响。我们的模型提供了多个可测试的预测，并表明致癌突变的不同时间序列可能导致肿瘤发生。最后，我们得出结论，四到五种致癌突变足以形成神经胶质瘤。
Glioma is the most common form of primary brain tumor. Demographically, the risk of occurrence increases until old age. Here we present a novel computational model to reproduce the probability of glioma incidence across the lifespan. Previous mathematical models explaining glioma incidence are framed in a rather abstract way, and do not directly relate to empirical findings. To decrease this gap between theory and experimental observations, we incorporate recent data on cellular and molecular factors underlying gliomagenesis. Since evidence implicates the adult neural stem cell as the likely cell-of-origin of glioma, we have incorporated empirically-determined estimates of neural stem cell number, cell division rate, mutation rate and oncogenic potential into our model. We demonstrate that our model yields results which match actual demographic data in the human population. In particular, this model accounts for the observed peak incidence of glioma at approximately 80 years of age, without the need to assert differential susceptibility throughout the population. Overall, our model supports the hypothesis that glioma is caused by randomly-occurring oncogenic mutations within the neural stem cell population. Based on this model, we assess the influence of the (experimentally indicated) decrease in the number of neural stem cells and increase of cell division rate during aging. Our model provides multiple testable predictions, and suggests that different temporal sequences of oncogenic mutations can lead to tumorigenesis. Finally, we conclude that four or five oncogenic mutations are sufficient for the formation of glioma.
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宇宙（癌症中的体细胞突变目录）数据库和网站。
影响因子：
8.8
作者：
Bamford, S;Dawson, E;Forbes, S;Clements, J;Pettett, R;Dogan, A;Flanagan, A;Teague, J;Futreal, PA;Stratton, MR;Wooster, R
通讯作者：
Wooster, R
肿瘤基因对神经元和星形胶质细胞的去分化会在小鼠中诱导神经胶质瘤。
DOI：
10.1126/science.1226929
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Friedmann-Morvinski D;Bushong EA;Ke E;Soda Y;Marumoto T;Singer O;Ellisman MH;Verma IM
通讯作者：
Verma IM
影响因子：
15.9
作者：
Dolecek, Therese A.;Propp, Jennifer M.;Kruchko, Carol
通讯作者：
Kruchko, Carol
影响因子：
7.8
作者：
Bailey, KJ;Maslov, AY;Pruitt, SC
通讯作者：
Pruitt, SC
影响因子：
64.8
作者：
Jeong, H;Mason, SP;Oltvai, ZN
通讯作者：
Oltvai, ZN