Chromosomal Rearrangements and Altered Nuclear Organization: Recent Mechanistic Models in Cancer

The last decade has seen significant progress in understanding how the genome is organized spatially within interphase nuclei. Recent analyses have confirmed earlier molecular cytogenetic studies on chromosome positioning within interphase nuclei and provided new information about the topologically...

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Bibliographic Details
Published in:Cancers 2021-11, Vol.13 (22), p.5860
Main Authors: Federico, Concetta, Bruno, Francesca, Ragusa, Denise, Clements, Craig S., Brancato, Desiree, Henry, Marianne P., Bridger, Joanna M., Tosi, Sabrina, Saccone, Salvatore
Format: Article
Language:English
Subjects:
Cancer
Cell differentiation
Chromatin
Chromosome rearrangements
Chromosome translocations
Chromosomes
Cytogenetics
Gene expression
Gene loci
Gene regulation
Genetic disorders
Genomes
Interphase
Nuclei
Reptiles & amphibians
Review
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Summary:The last decade has seen significant progress in understanding how the genome is organized spatially within interphase nuclei. Recent analyses have confirmed earlier molecular cytogenetic studies on chromosome positioning within interphase nuclei and provided new information about the topologically associated domains (TADs). Examining the nuances of how genomes are organized within interphase nuclei will provide information fundamental to understanding gene regulation and expression in health and disease. Indeed, the radial spatial positioning of individual gene loci within nuclei has been associated with up- and down-regulation of specific genes, and disruption of normal genome organization within nuclei will result in compromised cellular health. In cancer cells, where reorganization of the nuclear architecture may occur in the presence of chromosomal rearrangements such as translocations, inversions, or deletions, gene repositioning can change their expression. To date, very few studies have focused on radial gene positioning and the correlation to gene expression in cancers. Further investigations would improve our understanding of the biological mechanisms at the basis of cancer and, in particular, in leukemia initiation and progression, especially in those cases where the molecular consequences of chromosomal rearrangements are still unclear. In this review, we summarize the main milestones in the field of genome organization in the nucleus and the alterations to this organization that can lead to cancer diseases.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13225860