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The cancer aneuploidy paradox: In the light of evolution

The cancer aneuploidy paradox: In the light of evolution
The cancer aneuploidy paradox: In the light of evolution
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.
2073-4425
1-22
Salmina, Kristine
00a98b4d-8de8-4e78-99f7-a8834851d209
Huna, Anda
237bfd00-007b-4f76-a34f-a0cef3e95e36
Kalejs, Martins
74194c4c-fdb4-4fd7-b25d-f46ab5f0cc4b
Pjanova, Dace
cc905f38-5439-47da-b4ba-6e1311fa6785
Scherthan, Harry
ed4655f8-e9e1-49dd-b614-3bce67ec507c
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Erenpreisa, Jekaterina
70b5fecb-7208-431f-bd35-ec498edc0033
Salmina, Kristine
00a98b4d-8de8-4e78-99f7-a8834851d209
Huna, Anda
237bfd00-007b-4f76-a34f-a0cef3e95e36
Kalejs, Martins
74194c4c-fdb4-4fd7-b25d-f46ab5f0cc4b
Pjanova, Dace
cc905f38-5439-47da-b4ba-6e1311fa6785
Scherthan, Harry
ed4655f8-e9e1-49dd-b614-3bce67ec507c
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Erenpreisa, Jekaterina
70b5fecb-7208-431f-bd35-ec498edc0033

Salmina, Kristine, Huna, Anda, Kalejs, Martins, Pjanova, Dace, Scherthan, Harry, Cragg, Mark and Erenpreisa, Jekaterina (2019) The cancer aneuploidy paradox: In the light of evolution. Genes, 10 (2), 1-22, [83]. (doi:10.3390/genes10020083).

Record type: Article

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.

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Accepted/In Press date: 22 January 2019
e-pub ahead of print date: 25 January 2019

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Local EPrints ID: 428795
URI: http://eprints.soton.ac.uk/id/eprint/428795
ISSN: 2073-4425
PURE UUID: e3d5bedb-aecd-4224-9e05-4dcfa60931ab
ORCID for Mark Cragg: ORCID iD orcid.org/0000-0003-2077-089X

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Date deposited: 08 Mar 2019 17:30
Last modified: 22 Nov 2021 02:42

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Contributors

Author: Kristine Salmina
Author: Anda Huna
Author: Martins Kalejs
Author: Dace Pjanova
Author: Harry Scherthan
Author: Mark Cragg ORCID iD
Author: Jekaterina Erenpreisa

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