Functional variomics and network perturbation: connecting genotype to phenotype in cancer.
Functional variomics and network perturbation: connecting genotype to phenotype in cancer.
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DOI：
10.1038/nrg.2017.8
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Sahni N
中科院分区：
文献类型：
--
作者：
Yi S;Lin S;Li Y;Zhao W;Mills GB;Sahni N
蛋白质在复杂的细胞网络中与其他大分子相互作用，进行信号转导和生物学功能。在癌症中，遗传畸变传统上被认为会破坏整个基因功能。越来越多的人认识到，基因的每个突变都可能对蛋白质功能或网络重新布线产生微妙但独特的影响，从而导致癌症患者群体的不同表型后果。在这篇综述中，我们讨论了目前对癌症遗传变异的理解，包括广泛的突变类型和信号网络背景下对基因功能的广泛机制影响。我们强调最近的进展，在计算和实验策略，研究不同的功能和表型的突变的碱基对分辨率的后果。这些信息对于理解癌症基因的复杂多效性效应至关重要，并提供了癌症基因型和表型之间的可能联系。癌症中突变的丰富性和异质性为理解其影响带来了挑战，但这种功能表征对于优化临床护理至关重要。在这篇综述中，作者讨论了不同的计算工具和实验策略，用于阐明癌症突变的功能影响，包括对基因调控，蛋白质结构以及相互作用网络的局部和全局扰动的后果。
Proteins interact with other macromolecules in complex cellular networks for signal transduction and biological function. In cancer, genetic aberrations have been traditionally thought to disrupt the entire gene function. It has been increasingly appreciated that each mutation of a gene could have a subtle but unique effect on protein function or network rewiring, contributing to diverse phenotypic consequences across cancer patient populations. In this Review, we discuss the current understanding of cancer genetic variants including the broad spectrum of mutation classes and the wide range of mechanistic effects on gene function in the context of signaling networks. We highlight recent advances in computational and experimental strategies to study the diverse functional and phenotypic consequences of mutations at the base-pair resolution. Such information is critical for understanding the complex pleiotropic effect of cancer genes, and provides a possible link between genotype and phenotype in cancer. The abundance and heterogeneity of mutations in cancer create challenges for understanding their effects, but such functional characterization will be crucial for optimizing clinical care. In this Review, the authors discuss diverse computational tools and experimental strategies for elucidating the functional effects of cancer mutations, including consequences on gene regulation, protein structure, and local and global perturbations of interaction networks.
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发表时间：
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期刊：
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