Nuclear imaging in three dimensions: A unique tool in cancer research

Tumorigenesis includes alterations in the three-dimensional (3D) nuclear organization of the genome. The combination of sensitive quantitative fluorescent in situ hybridization (Q-FISH) and three-dimensional (3D) microscopy have evolved as powerful tools in studying the dynamic 3D organization of telomeres and chromosomes in the interphase nucleus of individual normal and tumor cells. Tumor-specific alterations in 3D telomere architecture, particularly the appearance of telomeric aggregates, are early events in tumorigenesis and have diagnostic and prognostic value. Novel tools in the 3D nuclear imaging arsenal now include high-throughput scanning capabilities and new 3D nano-resolution microscopy of tissues and cells. In this review, we summarize our current understanding of the biology of telomeres in the context of tumorigenesis and elucidate the important integrating function of advanced 3D imaging technologies in translating new discoveries in basic cancer research into new diagnostic tools for clinical oncologists to improve patient care.