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Genes (Basel). 2019 Jan 25;10(2). pii: E83. doi: 10.3390/genes10020083.

The Cancer Aneuploidy Paradox: In the Light of Evolution.

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Latvian Biomedical Research and Study Centre, LV1067 Riga, Latvia.
Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France.
Riga Stradins University, LV1007 Riga, Latvia.
Latvian Biomedical Research and Study Centre, LV1067 Riga, Latvia.
Bundeswehr Institute of Radiobiology affil. to the Univ. of Ulm, 80937 Munich, Germany.
Centre for Cancer Immunology, University of Southampton, Southampton SO16 6YD, UK.
Latvian Biomedical Research and Study Centre, LV1067 Riga, Latvia.


Aneuploidy should compromise cellular proliferation but paradoxically favours tumour progression and poor prognosis. Here, we consider this paradox in terms of our most recent observations of chemo/radio-resistant cells undergoing reversible polyploidy. The latter perform the segregation of two parental groups of end-to-end linked dyads by pseudo-mitosis creating tetraploid cells through a dysfunctional spindle. This is followed by autokaryogamy and a homologous pairing preceding a bi-looped endo-prophase. The associated RAD51 and DMC1/γ-H2AX double-strand break repair foci are tandemly situated on the AURKB/REC8/kinetochore doublets along replicated chromosome loops, indicative of recombination events. MOS-associated REC8-positive peri-nucleolar centromere cluster organises a monopolar spindle. The process is completed by reduction divisions (bi-polar or by radial cytotomy including pedogamic exchanges) and by the release of secondary cells and/or the formation of an embryoid. Together this process preserves genomic integrity and chromosome pairing, while tolerating aneuploidy by by-passing the mitotic spindle checkpoint. Concurrently, it reduces the chromosome number and facilitates recombination that decreases the mutation load of aneuploidy and lethality in the chemo-resistant tumour cells. This cancer life-cycle has parallels both within the cycling polyploidy of the asexual life cycles of ancient unicellular protists and cleavage embryos of early multicellulars, supporting the atavistic theory of cancer.


aneuploidy; autokaryogamy; cancer; chromothripsis; cleavage embryo; disabled spindle; meio-mitosis; recombination on kinetochores; reduction; somatic pairing

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