[Origin and role of aneuploidy in cancer].
Genetic aberrations of cancer cells have a profound impact for prognosis in several malignant neoplasias. The understanding of their origin is the basis for the development of new therapeutic options. Aneuploidy is observed in a large variety of premalignancies and tumors. Aneuploid cells harbor less or more than 46 chromosomes. The exact role of aneuploidy in tumorigenesis is still not clear. It has long been debated, whether aneuploidy directly contributes to tumorigenesis or reflects nonspecific changes during tumor progression. Several mechanisms are thought to be responsible for the generation of aneuploid sets of chromosomes: these comprise failure in cell division, such as defective chromosome separation caused by compromised mitotic checkpoint signaling or centrosome aberrations. Moreover, telomere shortening and defective DNA-damage signaling appear to be powerful driving forces of genomic instability. The loss of telomere sequences at the end of each chromosome and DNA double-strand breakage accompanied by compromised damage signaling favor fusion of chromosomes and generation of aneuploidy. Furthermore, aneuploidy arises to a much higher degree from a tetraploid state when compared to diploid cells. The frequent observation of the described defects in pre- and malignant cells supports the hypothesis that aneuploidy contributes to tumorigenesis.
Schnerch
D
D
Abteilung Innere Medizin I, Schwerpunkt Hämatologie/Onkologie, Medizinische Universitätsklinik, Freiburg.
Hasskarl
J
J
Engelhardt
M
M
Wäsch
R
R
D000782:Aneuploidy; D018385:Centrosome / Q000473:pathology; D002869:Chromosome Aberrations; D006801:Humans; D009369:Neoplasms / Q000235:genetics*