The cancer aneuploidy paradox: In the light of evolution

Kristine Salmina, Anda Huna, Martins Kalejs, Dace Pjanova, Harry Scherthan, Mark S. Cragg, Jekaterina Erenpreisa

    Research output: Contribution to journalArticlepeer-review

    32 Citations (Scopus)
    1 Downloads (Pure)

    Abstract

    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.

    Original languageEnglish
    Article number83
    Number of pages22
    JournalGenes
    Volume10
    Issue number2
    DOIs
    Publication statusPublished - 1 Jan 2019

    Keywords*

    • Aneuploidy
    • Autokaryogamy
    • Cancer
    • Chromothripsis
    • Cleavage embryo
    • Disabled spindle
    • Meio-mitosis
    • Recombination on kinetochores
    • Reduction
    • Somatic pairing

    Field of Science*

    • 3.1 Basic medicine
    • 3.2 Clinical medicine

    Publication Type*

    • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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