Polyploidy as an Adaptation against Loss of Heterozygosity in Cancer
Polyploidy is common in cancer cells and has implications for tumor progression and resistance to therapies, but it is unclear whether it is an adaptation of the tumor or the non-adaptive effect of genomic instability. I discuss the possibility that polyploidy reduces the deleterious effects of loss...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8528 |
| _version_ | 1797441801871687680 |
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| author | Marco Archetti |
| author_facet | Marco Archetti |
| author_sort | Marco Archetti |
| collection | DOAJ |
| description | Polyploidy is common in cancer cells and has implications for tumor progression and resistance to therapies, but it is unclear whether it is an adaptation of the tumor or the non-adaptive effect of genomic instability. I discuss the possibility that polyploidy reduces the deleterious effects of loss of heterozygosity, which arises as a consequence of mitotic recombination, and which in diploid cells leads instead to the rapid loss of complementation of recessive deleterious mutations. I use computational predictions of loss of heterozygosity to show that a population of diploid cells dividing by mitosis with recombination can be easily invaded by mutant polyploid cells or cells that divide by endomitosis, which reduces loss of complementation, or by mutant cells that occasionally fuse, which restores heterozygosity. A similar selective advantage of polyploidy has been shown for the evolution of different types of asexual reproduction in nature. This provides an adaptive explanation for cyclical ploidy, mitotic slippage and cell fusion in cancer cells. |
| first_indexed | 2024-03-09T12:31:20Z |
| format | Article |
| id | doaj.art-1433e4eea8fb417399fc95ff2b81955b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:31:20Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1433e4eea8fb417399fc95ff2b81955b2023-11-30T22:29:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315852810.3390/ijms23158528Polyploidy as an Adaptation against Loss of Heterozygosity in CancerMarco Archetti0Department of Biology, Pennsylvania State University, University Park, PA 16802, USAPolyploidy is common in cancer cells and has implications for tumor progression and resistance to therapies, but it is unclear whether it is an adaptation of the tumor or the non-adaptive effect of genomic instability. I discuss the possibility that polyploidy reduces the deleterious effects of loss of heterozygosity, which arises as a consequence of mitotic recombination, and which in diploid cells leads instead to the rapid loss of complementation of recessive deleterious mutations. I use computational predictions of loss of heterozygosity to show that a population of diploid cells dividing by mitosis with recombination can be easily invaded by mutant polyploid cells or cells that divide by endomitosis, which reduces loss of complementation, or by mutant cells that occasionally fuse, which restores heterozygosity. A similar selective advantage of polyploidy has been shown for the evolution of different types of asexual reproduction in nature. This provides an adaptive explanation for cyclical ploidy, mitotic slippage and cell fusion in cancer cells.https://www.mdpi.com/1422-0067/23/15/8528polyploidyheterozygositycomplementationendomitosiscancer |
| spellingShingle | Marco Archetti Polyploidy as an Adaptation against Loss of Heterozygosity in Cancer International Journal of Molecular Sciences polyploidy heterozygosity complementation endomitosis cancer |
| title | Polyploidy as an Adaptation against Loss of Heterozygosity in Cancer |
| title_full | Polyploidy as an Adaptation against Loss of Heterozygosity in Cancer |
| title_fullStr | Polyploidy as an Adaptation against Loss of Heterozygosity in Cancer |
| title_full_unstemmed | Polyploidy as an Adaptation against Loss of Heterozygosity in Cancer |
| title_short | Polyploidy as an Adaptation against Loss of Heterozygosity in Cancer |
| title_sort | polyploidy as an adaptation against loss of heterozygosity in cancer |
| topic | polyploidy heterozygosity complementation endomitosis cancer |
| url | https://www.mdpi.com/1422-0067/23/15/8528 |
| work_keys_str_mv | AT marcoarchetti polyploidyasanadaptationagainstlossofheterozygosityincancer |