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Classification of chromosome segregation errors in cancer

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Abstract

Abnormal chromosome segregation at mitosis is one way by which neoplastic cells accumulate the many genetic abnormalities required for tumour development. In this paper, a straightforward morphology-based classification of chromosome segregation errors in cancer is suggested. This classification distinguishes between abnormalities in spindle symmetry (spindle multipolarity, size-asymmetry of ana-telophase poles) and abnormalities in sister chromatid segregation (chromosome bridges, chromatid bridges, chromosome lagging, acentric fragment lagging). Often, these categories of errors must be combined to accurately describe the events in a single abnormal mitotic cell. The suggested categories can to some extent be distinguished by standard chromatin staining. However, labelling of abnormal mitotic figures by fluorescence in situ hybridization and immunofluorescence enhances the accuracy of classification and also allows visualisation of the segregation of individual chromosomes, making it possible to detect non-disjunction also in the absence of gross alterations in mitotic morphology. Further characterisation of the molecular alterations leading to abnormal chromosome segregation together with the current developments in nano-level and real-time imaging will undoubtedly lead to an improved understanding of chromosome dynamics in cancer cells. Any morphology-based classification of chromosome segregation errors in cancer must therefore be taken as provisional, anticipating a satisfactory integration of morphology and molecular biology.

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Acknowledgments

The author is grateful to Prof N. Mandahl for critical reading of the manuscript. The author is supported by the Swedish Children’s Cancer Foundation, the Swedish Cancer Society, the Swedish Research Council, the Swedish Medical Society, the Lund University Hospital Donation Funds, the Gunnar Nilsson Cancer Foundation, the Medical Faculty of Lund University, the Crafoord Foundation, the Erik-Philip Sörensen Foundation, and the Lundgren Foundation.

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Correspondence to David Gisselsson.

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Communicated by E.A. Nigg

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Gisselsson, D. Classification of chromosome segregation errors in cancer. Chromosoma 117, 511–519 (2008). https://doi.org/10.1007/s00412-008-0169-1

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