Lab of Bioinformatics and Systems Biology, National Research Council Canada, Montreal, Canada; McGill University Center for Bioinformatics, Montreal, Canada.
Cancer Lett. 2013 Nov 1;340(2):261-9. doi: 10.1016/j.canlet.2012.11.050. Epub 2012 Dec 22.
In recent years, cancer genome sequencing and other high-throughput studies of cancer genomes have generated many notable discoveries. In this review, novel genomic alteration mechanisms, such as chromothripsis (chromosomal crisis) and kataegis (mutation storms), and their implications for cancer are discussed. Genomic alterations spur cancer genome evolution. Thus, the relationship between cancer clonal evolution and cancer stems cells is commented. The key question in cancer biology concerns how these genomic alterations support cancer development and metastasis in the context of biological functioning. Thus far, efforts such as pathway analysis have improved the understanding of the functional contributions of genetic mutations and DNA copy number variations to cancer development, progression and metastasis. However, the known pathways correspond to a small fraction, plausibly 5-10%, of somatic mutations and genes with an altered copy number. To develop a comprehensive understanding of the function of these genomic alterations in cancer, an integrative network framework is proposed and discussed. Finally, the challenges and the directions of studying cancer omic data using an integrative network approach are commented.
近年来，癌症基因组测序和其他高通量的癌症基因组研究已经产生了许多显著的发现。在这篇综述中，讨论了新颖的基因组改变机制，如染色体重排（染色体危机）和kataegis（突变风暴），以及它们对癌症的影响。基因组改变激发了癌症基因组的进化。因此，评论了癌症克隆进化与癌症干细胞之间的关系。癌症生物学中的关键问题是，在生物学功能的背景下，这些基因组改变如何支持癌症的发展和转移。到目前为止，通路分析等努力已经提高了对遗传突变和 DNA 拷贝数变异对癌症发展、进展和转移的功能贡献的理解。然而，已知的通路仅对应于体细胞突变和拷贝数改变的基因的一小部分，合理的范围是 5-10%。为了全面了解这些基因组改变在癌症中的功能，提出并讨论了一个综合网络框架。最后，评论了使用综合网络方法研究癌症组学数据的挑战和方向。
