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Open AccessArticle

The Cancer Aneuploidy Paradox: In the Light of Evolution

Latvian Biomedical Research and Study Centre, LV1067 Riga, Latvia
Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France
Scientific Laboratory of Biomechanics, Riga Stradins University, LV1007 Riga, Latvia
Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, 80937 Munich, Germany
Centre for Cancer Immunology, University of Southampton, Southampton SO16 6YD, UK
Author to whom correspondence should be addressed.
Genes 2019, 10(2), 83;
Received: 7 January 2019 / Revised: 21 January 2019 / Accepted: 22 January 2019 / Published: 25 January 2019
(This article belongs to the Special Issue Chromosomal Heterogeneity and Human Diseases)
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. View Full-Text
Keywords: cancer; aneuploidy; meio-mitosis; disabled spindle; autokaryogamy; somatic pairing; recombination on kinetochores; reduction; chromothripsis; cleavage embryo cancer; aneuploidy; meio-mitosis; disabled spindle; autokaryogamy; somatic pairing; recombination on kinetochores; reduction; chromothripsis; cleavage embryo
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Salmina, K.; Huna, A.; Kalejs, M.; Pjanova, D.; Scherthan, H.; Cragg, M.S.; Erenpreisa, J. The Cancer Aneuploidy Paradox: In the Light of Evolution. Genes 2019, 10, 83.

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