To see an interphase chromosome or: How a disease can be associated with specific nuclear genome organization

Abstract

The last hierarchical level of cellular genome organization is the spatial arrangement of chromosomes within the nuclear space. Despite of high regulatory potential and functional implications, issues concerning nuclear organization at chromosomal level are rarely addressed because of limitations in visualizing interphase chromosomes. The problem is especially seen when an attempt to associate specific patterns of nuclear genome organization with a pathological condition is made. Fortunately, advances in molecular cytogenetics have provided for a solution to visualize chromosomes in interphase nuclei at molecular resolution. A study in this issue of BioDiscovery shows the way of how to identify interphase chromosome architecture at molecular resolutions and demonstrates the involvement of specific nuclear genome organization in generating a cancercausing chromosomal aberration (translocation between chromosomes 8 and 21 in acute myelogenous leukemia). Authors' findings suggest interphase molecular cytogenetic techniques (i.e. interphase chromosome-specific multicolor banding or ICS-MCB) to be required to perform studies regarding nuclear genome organization at chromosomal level and its role in disease pathogenesis.

Distinct and shared three‐dimensional chromosome organization patterns in lymphocytes, monoclonal gammopathy of undetermined significance and multiple myeloma

“…Previous studies revealed the consistent association of specific chromosomal abnormalities with specific types of cancer, supporting the hypothesis that these nonrandom structural chromosomal abnormalities are the cause of malignant transformation in a particular cancer type . Advances in molecular cytogenetics have provided knowledge about chromatin organization in interphase nuclei at molecular resolution . It was proposed for a long time that neighboring chromosomes/gene loci may engage in translocations more frequently than chromosomes/loci that are found at larger distances to each other .…”

“…The distributions of particular chromosomes were observed for both, the myeloma cells as well as the normal B-lymphocytes. The two-sided, two-sample Kolmogorov-Smirnov (KS) analysis showed significant changes in the relative radial positions of chromosome 4,9,11,14,16 and 18 between lymphocyte and myeloma nuclei ( Table 3). In contrast, there were no significant alterations in the relative radial position of chromosome 19 and 22, which were located toward a more central position within the cell nucleus.…”

“…10 Advances in molecular cytogenetics have provided knowledge about chromatin organization in interphase nuclei at molecular resolution. 11 It was proposed for a long time that neighboring chromosomes/ gene loci may engage in translocations more frequently than chromosomes/loci that are found at larger distances to each other. 12 In fact, studies by several groups indicated that neighborhood relationships appear critical for translocations to occur.…”

Cytogenomic epileptology

“…In fact, neurocytogenetic analysis of nuclear organization in the unaffected and diseased brain has never been systematically performed. Current molecular cytogenetics and cytogenomics possess technological possibilities to perform high-resolution analysis of chromosomal arrangements and rearrangements in postmitotic cells of the human brain [139][140][141][142]. The analysis of brain-specific chromosomal nuclear organization appears even more attractive taking into account that spatial positioning of chromosomes determines behavior and stability of the nuclear genome in an interphase nucleus [140,142,143].…”