Cancer genome sequencing: the challenges ahead
Cancer genome sequencing: the challenges ahead
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DOI：
10.1002/bies.20610
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发表时间：
2007-08-01
期刊：
影响因子：
4
通讯作者：
Heng, Henry H. Q.
中科院分区：
文献类型：
--
作者：
Heng, Henry H. Q.
癌症基因组图谱(TCGA)计划的一个主要挑战是解决癌症的高度遗传和表观遗传异质性。对于大多数实体肿瘤来说，演变模式是随机的，最终产物是不可预测的，这与许多血液学癌症经典描述的相对可预测的逐步模式形成对比。此外，在癌症中产生异常水平的系统异质性的主导因素是基因组异常，而不是基因突变。癌症的这些特征可以显著降低测序方法的影响，因为只有当突变基因是癌症的主要原因时，直接对它们进行测序才是合理的。许多生物因素(遗传和表观遗传变异、代谢过程)和环境影响会增加癌症形成的可能性，这取决于特定的情况。这些因素之间的共同联系是随机基因组变异，这些随机基因组变异在生物系统的多个水平上提供了癌症进化过程背后的驱动力。IS分析表明，癌症是一种概率疾病，TCGA项目最具挑战性的问题以及抗击癌症的一般战略的制定，存在于概念层面。《生物文集》29：783794,2007年。(C)2007年威利期刊公司。
A major challenge for The Cancer Genome Atlas (TCGA) Project is solving the high level of genetic and epigenetic heterogeneity of cancer. For the majority of solid tumors, evolution patterns are stochastic and the end products are unpredictable, in contrast to the relatively predictable stepwise patterns classically described in many hematological cancers. Further, it is genome aberrations, rather than gene mutations, that are the dominant factor in generating abnormal levels of system heterogeneity in cancers. These features of cancer could significantly reduce the impact of the sequencing approach, as it is only when mutated genes are the main cause of cancer that directly sequencing them is justified. Many biological factors (genetic and epigenetic variations, metabolic processes) and environmental influences can increase the probability of cancer formation, depending on the given circumstances. The common link between these factors is the stochastic genome variations that provide the driving force behind the cancer evolutionary process within multiple levels of a biological system. is analysis suggests that cancer is a disease of probability and the most-challenging issue to the TCGA project, as well as the development of general strategies for fighting cancer, lie at the conceptual level. BioEssays 29:783794, 2007. (c) 2007 Wiley Periodicals, Inc.