Oncogenic remodeling of the three-dimensional organization of the interphase nucleus: c-Myc induces telomeric aggregates whose formation precedes chromosomal rearrangements.

The three-dimensional (3D) organization of the normal interphase nucleus permits the regulated completion of transcription and replication and assures proper chromosome organization. Aberrations from the normal 3D structural order of the nucleus are found in tumor cells. When examining the 3D organization of telomeres in nuclei of normal and tumor cells, we found that telomeres of normal nuclei do not overlap, while telomeres of tumor cells form aggregates of various numbers and sizes. To understand how such changes occur and what their implications are we have recently examined the role of the oncoprotein c-Myc in inducing changes in the 3D nuclear organization of telomeres. We found that c-Myc remodels the organization of telomeres and chromosomes in the interphase nucleus. It induces the formation of telomeric aggregates and fusions that are followed by breakage-bridge fusion cycles, and lead to the onset of chromosomal rearrangements that are typical of tumor cells.