During interphase, chromosomes occupy non-random positions within the nuclear space. Interphase chromosome arrangement is considered to play significant role in development and disease mediated by regulation of genome expression and stability maintenance [1, 2]. However, some technical limitations in analyzing chromosome arrangement and positioning (visualizing interphase chromosomes) hinder the progress in studying nuclear genome organization. More precisely, the availability to visualize either specific genomic loci or ambiguous chromosome territories was found to be insufficient for interphase cytogenetics. To solve this problem, a technique providing for simultaneous visualization of the whole chromosome and its regions in a given nucleus has appeared to be required . The development of interphase chromosome-specific multicolor banding (ICS-MCB) has led the way towards the high-resolution interphase cytogenetic analysis for studying chromosomal numbers, structure and spatial arrangement within the nucleus [4-7]. Using ICS-MCB, chromosome architecture was evaluated in some tissues at “subchromosomal” resolution and specific positioning of chromosomal loci was shown to be linked to generation and behavior of rearranged chromosomes in interphase [8-10]. Interestingly, specific chromosome positioning was previously suggested to predispose to cancer-causing chromosomal aberrations . Unfortunately, convincing proofs were not obtained because the data were usually acquired by techniques painting chromosome territories without an integral view of the whole chromosome.
The present issue of BioDiscovery
reports an investigation of interphase chromosome architecture in acute
myelogenous leukemia by ICS-MCB and its relation to causative
translocation between chromosomes 8 and 21 .
In the light of authors’ findings, it seems pertinent to pay attention
to technological aspects of interphase molecular cytogenetics, which are
important for interpreting data on nuclear genome organization.
Additionally, these aspects are also significant for understanding how a
disease can be associated with specific nuclear genome organization
allowing speculations about the implications of similar studies for the
definition of disease pathways including genetic-environmental
interactions and the development of molecular therapies.
Visualizing interphase chromosomes
The interphase chromosome architecture is commonly determined through application of FISH (fluorescence in situ hybridization)-based techniques. As noted below, interphase molecular cytogenetic techniques are usually applied either for analysis of specific genomic loci (using probes for relatively small DNA sequences (rarely >1Mb) comparing to the whole chromosomes) or for painting the whole chromosome, visualized as a chromosome territory (reviewed in ). Although these approaches are successfully applied for studying chromosomal numbers and intranuclear arrangement, the impossibility to identify positioning of specific chromosomal regions in relation to the chromosome itself and to other chromosomal regions significantly reduces the resolution of interphase chromosomal analysis . Three dimensional (3D) FISH allowing the visualization of chromosomes as volume structures provides for examining chromosomal positioning relative to nuclear structures (i.e. nuclear membrane, nucleolus etc.) (reviewed in ). Alternatively, current approaches towards studying DNA-based structure of chromosomes can depict locus positioning in four dimensions (space and time), which is relevant not only to basic principles of interphase genome organization, but also to chromosome arrangement in cancer cells . Still, one has to operate with data on arrangement of specific chromosomal loci or ambiguous chromosome territories without an integral view of the whole chromosome at molecular resolution.
ICS-MCB is an intriguing alternative to the aforementioned approaches, since it gives an opportunity to determine structure and arrangement of differentially painted chromosomal regions. Its application allows the analysis of chromosome (chromosomal loci) positioning in interphase and chromosomal associations at “subchromosomal” resolution in a given nucleus (for more details see [4-9]). Evidently, analyzing each chromosomal region is likely to provide more reliable information in contrast to analyzing homogenously painted chromosomes or a single chromosomal region. The article by Dr. Liehr and colleagues in this issue of BioDiscovery  continues the line of research on nuclear chromosome organization performed by ICS-MCB. Again, this technique has been demonstrated effective for examination of interphase chromosome architecture. Furthermore, this state-of-the-art technique in combination with FISH using gene-specific probes has allowed authors to show the involvement of specific interphase chromosome organization in promoting the typical translocation between chromosomes 8 and 21 leading to acute myelogenous leukemia.
Nuclear genome/chromosome organization and disease
Since the introduction of interphase molecular cytogenetics a significant effort has been made to provide comprehensive information about the meaning of nuclear genome (chromosome) organization [1-3, 13-15]. As a result, interphase chromosome architecture was demonstrated to be involved in critical nuclear processes, which are relevant to cellular homeostasis in health and disease (Box 1).