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

Abstract

The consistent appearance of specific chromosomal translocations in multiple myeloma has suggested that the positioning of chromosomes in the interphase nucleus might play a role in the occurrence of particular chromosomal rearrangements associated with malignant transformation. Using fluorescence in situ hybridization, we have determined the positions of selected chromosome pairs (18 and 19, 9 and 22, 4 and 14, 14 and 16, 11 and 14) in interphase nuclei of myeloma cells compared to normal lymphocytes of treatment‐naïve patients. All chromosome pairs were arranged in a nonrandom pattern. Chromosomes commonly involved in myeloma‐associated translocations (4 and 14, 14 and 16, 11 and 14) were found in close spatial proximity, and this is correlated with the occurrence of overlapping chromosome territories. The spatial distribution of chromosomes may increase the possibility of chromosomal translocations in multiple myeloma.

Intermingling of chromosome territories

“…This suggests that the spatial distribution of chromosomes may increase the possibility of chromosomal translocations in MM. By contrast, chromosome 18 and 19 territories have the largest distance among the five analyzed pairs of chromosomes and they are not usually engaged in translocations in myeloma …”

Super-resolution binding activated localization microscopy through reversible change of DNA conformation

“…It is anticipated that the discrimination power of nuclear texture analysis will be substantially improved when nuclear chromatin structures are imaged at enhanced resolution. In line with this, another super-resolution microscopy technique termed 3D-SIM has already been employed to quantitatively assess differences in nuclear structure in Hodgkin's lymphoma [ 41 , 42 ], Multiple Myeloma (MM) [ 43 , 44 ], and in Alzheimer's disease [ 45 ], all obtained from patients. Whereas 3D-SIM of DAPI labeled DNA provides resolution in the order of 100 nm, fBALM could improve it further by another factor of ∼2 (i.e.…”

MYCN overexpression is linked to significant differences in nuclear DNA organization in neuroblastoma

“…The three-dimensional nanometer-scale resolution enabled by 3D SIM has transformed our understanding of DNA structure, allowing visualization of chromatin distribution within the cell nucleus inaccessible to conventional light optical techniques [18][19][20][21][22]. Super-resolution (SR) imaging has evolved from a tool built and used by physicists, to a commercially available imaging system that is now more broadly applied to multiple fields, especially in the past decade when it became obvious that sub-Abbe resolution of cellular structures became feasible and enhanced our knowledge of structures in cells dramatically [23][24][25].…”

“…Analysis of nuclear chromatin distribution has been proven to be a highly effective tool to quantify changes in chromatin architecture associated with malignancy and disease progression [20][21][22]. The value of super-resolution microscopy technique in assessing and quantifying differences in nuclear structure between normal and disease cells has already been demonstrated in Hodgkin's lymphoma, multiple myeloma and in Alzheimer's disease [12,[18][19][21][22]. The first comprehensive 3D SIM studies investigating the 3D nuclear DNA organization in cancer and addressing the changes in the organization were performed by our group [12,16,17].…”