Heng Henry H Q, Liu Guo, Bremer Steven, Ye Karen J, Stevens Joshua, Ye Christine J
Center for Molecular Medicine and Genetics, Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
Genome. 2006 Mar;49(3):195-204. doi: 10.1139/g06-023.
The theoretical view that genome aberrations rather than gene mutations cause a majority of cancers has gained increasing support from recent experimental data. Genetic aberration at the chromosome level is a key aspect of genome aberration and the systematic definition of chromosomal aberrations with their impact on genome variation and cancer genome evolution is of great importance. However, traditionally, efforts have focused on recurrent clonal chromosome aberrations (CCAs). The significance of stochastic non-clonal chromosome aberrations (NCCAs) is discussed in this paper with emphasis on the simple types of NCCAs that have until recently been considered "non-significant background". Comparison of various subtypes of transitional and late-stage CCAs with simple and complex types of NCCAs has uncovered a dynamic relationship among NCCAs, CCAs, overall genomic instability, and karyotypic evolution, as well as the stochastic nature of cancer evolution. Here, we review concepts and methodologies to measure NCCAs and discuss the possible causative mechanism and consequences of NCCAs. This study raises challenging questions regarding the concept of cancer evolution driven by stochastic chromosomal aberration mediated genome irregularities that could have repercussions reaching far beyond cancer and organismal genomes.
基因组畸变而非基因突变导致大多数癌症的理论观点，已从最近的实验数据中获得了越来越多的支持。染色体水平的遗传畸变是基因组畸变的一个关键方面，系统地定义染色体畸变及其对基因组变异和癌症基因组进化的影响至关重要。然而，传统上，研究重点一直放在复发性克隆染色体畸变（CCA）上。本文讨论了随机非克隆染色体畸变（NCCA）的意义，重点是直到最近还被视为“无显著意义背景”的简单类型的NCCA。将过渡性和晚期CCA的各种亚型与简单和复杂类型的NCCA进行比较，揭示了NCCA、CCA、整体基因组不稳定性和核型进化之间的动态关系，以及癌症进化的随机性。在这里，我们回顾了测量NCCA的概念和方法，并讨论了NCCA可能的致病机制和后果。这项研究提出了一些具有挑战性的问题，涉及由随机染色体畸变介导的基因组不规则性驱动的癌症进化概念，其影响可能远远超出癌症和生物体基因组。
