title: Why it is crucial to analyze non clonal chromosome aberrations or NCCAs?
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.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 USA ; Department of Pathology, Wayne State University School of Medicine, 3226 Scott Hall, 540 E. Canfield, Detroit, MI 48201 USA.
authors.forename: Henry H Q
authors.initials: HH
authors.lastname: Heng
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 USA ; Division of Graduate Medical Sciences, Boston University School of Medicine, Boston, MA 02118 USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Regan
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 USA.
authors.forename: Guo
authors.initials: G
authors.lastname: Liu
authors.affiliation: The Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI USA.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Ye
keywords: Clonal Chromosome Aberrations or CCAs; Fuzzy inheritance; Genome instability; Genome theory; Heterogeneity; NCCA/CCA cycle; Non Clonal Chromosome Aberrations or NCCAs; Parts inheritance; System inheritance