Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis.

Summary, in English

One extra chromosome copy (i.e., trisomy) is the most common type of chromosome aberration in cancer cells. The mechanisms behind the generation of trisomies in tumor cells are largely unknown, although it has been suggested that dysfunction of the spindle assembly checkpoint (SAC) leads to an accumulation of trisomies through failure to correctly segregate sister chromatids in successive cell divisions. By using Wilms tumor as a model for cancers with trisomies, we now show that trisomic cells can form even in the presence of a functional SAC through tripolar cell divisions in which sister chromatid separation proceeds in a regular fashion, but cytokinesis failure nevertheless leads to an asymmetrical segregation of chromosomes into two daughter cells. A model for the generation of trisomies by such asymmetrical cell division accurately predicted several features of clones having extra chromosomes in vivo, including the ratio between trisomies and tetrasomies and the observation that different trisomies found in the same tumor occupy identical proportions of cells and colocalize in tumor tissue. Our findings provide an experimentally validated model explaining how multiple trisomies can occur in tumor cells that still maintain accurate sister chromatid separation at metaphase-anaphase transition and thereby physiologically satisfy the SAC.

• Author: David Gisselsson Nord; Yuesheng Jin; David Lindgren; Johan Persson; Lennart Gisselsson; Sandra Hanks; Daniel Sehic; Linda Holmquist Mengelbier; Ingrid Øra; Nazneen Rahman; Fredrik Mertens; Felix Mitelman; Nils Mandahl
• Department/s: Division of Clinical Genetics; Department of Translational Medicine; Section IV; Paediatrics (Lund); Pathways of cancer cell evolution; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2010
• Language: English
• Pages: 20489-20493
• Publication/Series: Proceedings of the National Academy of Sciences
• Volume: 107
• Issue: 47
• Full text: - 3 MB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/21059955?dopt=Abstract; http://dx.doi.org/10.1073/pnas.1006829107
• Document type: Journal article
• Publisher: National Academy of Sciences
• Topic: Pediatrics; Medical Genetics; Neurology; Cancer and Oncology
• Status: Published
• Research group: Pathways of cancer cell evolution
• ISBN/ISSN/Other: ISSN: 1091-6490