A Paradoxical Role for Somatic Chromosomal Mosaicism and Chromosome Instability in Cancer: Theoretical and Technological Aspects.

ABSTRACT

Somatic chromosomal mosaicism, chromosome instability, and cancer are intimately linked together. Addressing the role of somatic genome variations (encompassing chromosomal mosaicism and instability) in cancer yields paradoxical results. Firstly, somatic mosaicism for specific chromosomal rearrangement causes cancer per se. Secondly, chromosomal mosaicism and instability are associated with a variety of diseases (chromosomal disorders demonstrating less severe phenotypes, complex diseases), which exhibit cancer predisposition. Chromosome instability syndromes may be considered the best examples of these diseases. Thirdly, chromosomal mosaicism and instability are able to result not only in cancerous diseases but also in non-cancerous disorders (brain diseases, autoimmune diseases, etc.). Currently, the molecular basis for these three outcomes of somatic chromosomal mosaicism and chromosome instability remains incompletely understood. Here, we address possible mechanisms for the aforementioned scenarios using a system analysis model. A number of theoretical models based on studies dedicated to chromosomal mosaicism and chromosome instability seem to be valuable for disentangling and understanding molecular pathways to cancer-causing genome chaos. In addition, technological aspects of uncovering causes and consequences of somatic chromosomal mosaicism and chromosome instability are discussed. In total, molecular cytogenetics, cytogenomics, and system analysis are likely to form a powerful technological alliance for successful research against cancer.