当前的细胞遗传学主要集中在鉴定复发性核型改变上,也称为克隆染色体畸变(CCA)。这样做的理由似乎很简单:反复发生的遗传变化与疾病或特定的生理状况有关,而非克隆染色体畸变(NCCAs)是微不足道的遗传背景或噪声。然而,在现实中,绝大多数染色体改变是NCCAs,在大多数实体瘤中鉴定共同共有的CCA是具有挑战性的。此外,核型,而不是基因,表示系统继承,或蓝图,并且每个NCCA代表改变的基因组系统。这些认识强调了在细胞遗传学分析中重新评估NCCA的重要性。在这篇概念文章中,我们简要回顾了NCCAs的定义,对它们的一些历史误解,以及为什么NCCA不是微不足道的噪音,“而是提供基因组异质性和复杂性的细胞群体的一个非常重要的特征,代表模糊继承的一种重要形式。NCCAs的频率也代表了测量内部和环境诱导的基因组不稳定性的指标。此外,NCCA/CCA周期与宏和微蜂窝演进有关。最后,在许多疾病/病症中观察到升高的NCCAs。考虑到所有这些因素,我们呼吁立即采取行动研究和报告NCCA。具体来说,需要努力表征和比较不同类型的NCCA,为了定义它们在各种组织中的基线,开发进入有丝分裂细胞的方法,重新检查/解释NCCA数据,并开发NCCA数据库。
Current cytogenetics has largely focused its efforts on the identification of recurrent karyotypic alterations, also known as clonal chromosomal aberrations (CCAs). The rationale of doing so seems simple: recurrent genetic changes are relevant for diseases or specific physiological conditions, while non clonal chromosome aberrations (NCCAs) are insignificant genetic background or noise. However, in reality, the vast majority of chromosomal alterations are NCCAs, and it is challenging to identify commonly shared CCAs in most solid tumors. Furthermore, the karyotype, rather than genes, represents the system inheritance, or blueprint, and each NCCA represents an altered genome system. These realizations underscore the importance of the re-evaluation of NCCAs in cytogenetic analyses. In this concept article, we briefly review the definition of NCCAs, some historical misconceptions about them, and why NCCAs are not insignificant \"noise,\" but rather a highly significant feature of the cellular population for providing genome heterogeneity and complexity, representing one important form of fuzzy inheritance. The frequencies of NCCAs also represent an index to measure both internally- and environmentally-induced genome instability. Additionally, the NCCA/CCA cycle is associated with macro- and micro-cellular evolution. Lastly, elevated NCCAs are observed in many disease/illness conditions. Considering all of these factors, we call for the immediate action of studying and reporting NCCAs. Specifically, effort is needed to characterize and compare different types of NCCAs, to define their baseline in various tissues, to develop methods to access mitotic cells, to re-examine/interpret the NCCAs data, and to develop an NCCA database.