Zender Lars, Lowe Scott W
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Curr Opin Oncol. 2008 Jan;20(1):72-6. doi: 10.1097/CCO.0b013e3282f31d5d.
The completion of the human genome project has enabled several new technologies for studying cancer genetics and cancer genomes. However, genomic instability and heterogeneity of human tumors impedes a straightforward cataloging of cancer genes and possible therapeutic targets. Strategies enabling the distinction of causal genetic alterations from bystander genomic noise are needed and should significantly speed up the process of cancer-gene discovery.
A series of recent papers described the development of integrative oncogenomic approaches based on innovative cancer mouse models and how these can be used to speed up the discovery of new cancer genes. In the presented studies, spontaneously acquired genetic alterations in mouse tumors of defined genetic origin are used to filter/prioritize relevant lesions from complex human cancer genomes. As will be discussed in this review, a great advantage of this approach is that pinpointed candidate genes can be functionally validated in the right genetic context in vivo, which significantly increases confidence for later therapeutic development efforts.
The discussed approaches hold great promise to speed up the process of cancer-gene discovery and should be considered to complement time-consuming and costly endeavors like the Cancer Genome Project.
人类基因组计划的完成催生了多种用于研究癌症遗传学和癌症基因组的新技术。然而，人类肿瘤的基因组不稳定性和异质性阻碍了对癌症基因及潜在治疗靶点进行直接编目。因此，需要能够区分因果性基因改变与旁观者基因组噪声的策略，这有望显著加速癌症基因的发现进程。
一系列近期论文描述了基于创新癌症小鼠模型的整合肿瘤基因组学方法的发展，以及如何利用这些方法加速新癌症基因的发现。在这些研究中，具有特定遗传起源的小鼠肿瘤中自发获得的基因改变被用于从复杂的人类癌症基因组中筛选/优先选择相关病变。正如本综述将要讨论的，这种方法的一个巨大优势在于，精准定位的候选基因能够在体内合适的遗传背景下进行功能验证，这显著增强了后续治疗开发工作的信心。
所讨论的方法在加速癌症基因发现进程方面具有巨大潜力，应被视为对像癌症基因组计划这样耗时且成本高昂的工作的补充。
