Abstract
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.
Highlights
Large scale –omics have revealed the surprising observation that stochastic alterations at various genetic and non-genetic levels are overwhelming [1]
We usually examine 50–100 mitotic figures when scoring non clonal chromosome aberrations (NCCAs) and clonal chromosomal aberrations (CCAs), and 4 % is used as the cut-off; this is done even though, theoretically, the cut-off line could be 1 % or lower
Our research has demonstrated that NCCAs are not “noise” after all, as NCCAs-formed genome heterogeneity is a key feature of the biological system that functions as a layer of complexity [1, 53, 54]
Summary
Large scale –omics have revealed the surprising observation that stochastic alterations at various genetic and non-genetic levels are overwhelming [1]. Since the variable karyotype serves as a good model to study fuzzy inheritance, the cytogenetics and cytogenomics field has positioned itself to tackle the important issue of how genome alteration unifies other types of molecular analyses, especially with the power of monitoring large number of individual cells within a defined cellular population.
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