Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Nat Rev Genet. 2017 Jul;18(7):395-410. doi: 10.1038/nrg.2017.8. Epub 2017 Mar 27.
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 signalling 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 crucial to understanding the complex pleiotropic effect of cancer genes and provides a possible link between genotype and phenotype in cancer.
蛋白质在复杂的细胞网络中与其他大分子相互作用，以进行信号转导和发挥生物功能。在癌症中，传统上认为遗传异常会破坏整个基因功能。人们越来越认识到，一个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中出现不同的表型后果。在这篇综述中，我们讨论了对癌症遗传变异的现有理解，包括广泛的突变类别和对信号网络中基因功能的多种机制影响。我们强调了在研究碱基对分辨率下突变的多种功能和表型后果的计算和实验策略的最新进展。这些信息对于理解癌症基因的复杂多效性效应至关重要，并为癌症中的基因型和表型之间提供了可能的联系。
