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| Status |
Public on Oct 21, 2020 |
| Title |
Spontaneous Cell Fusions as a Mechanism of Parasexual Recombination in Tumor Cell Populations. [2] |
| Organism |
Homo sapiens |
| Experiment type |
SNP genotyping by SNP array
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| Summary |
Initiation and progression of cancers reflect the underlying process of somatic evolution, which follows a Darwinian logic, i.e., diversification of heritable phenotypes provides a substrate for natural selection, resulting in the outgrowth of the most fit subpopulations. Although somatic evolution can tap into multiple sources of diversification, it is assumed to lack access to (para)sexual recombination – a key diversification mechanism throughout all strata of life. Based on observations of spontaneous fusions involving cancer cells, reported genetic instability of polypoid cells, and precedence of fusion-mediated parasexual recombination in fungi, we asked whether cell fusions could serve as a source of parasexual recombination in cancer cell populations. Using differentially labelled tumor cells, we found evidence of low-frequency, spontaneous cell fusions between carcinoma cells in multiple cell line models of breast cancer both in vitro and in vivo. While some hybrids remained polyploid, many displayed partial ploidy reduction, generating diverse progeny with heterogeneous inheritance of parental alleles, indicative of partial recombination. Hybrid cells also displayed elevated levels of phenotypic plasticity, which may further amplify the impact of cell fusions on the diversification of phenotypic traits. Using mathematical modeling, we demonstrated that the observed rates of spontaneous somatic cell fusions may enable populations of tumor cells to amplify clonal heterogeneity, thus facilitating the exploration of larger areas of the adaptive landscape, relative to strictly asexual populations, which may substantially accelerate a tumor’s ability to adapt to new selective pressures.
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| Overall design |
Illumina CytoNP arrays were performed according to the manufacturer's protocol. DNA was extracted from frosen cell pellet using Quiagen DNAeasy kit. 12 samples were analysed: 8 subclones of hybrid between SUM159 and MDA231 cell lines, 2 bulk samples from passage 3 ans passage 8 of hybrid SUM159-MDA231 cells. Parental cell lines: MDA231, SUM159. Cell were grown in correcponding media before collecting the samples, no treatment was applied.
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| Contributor(s) |
Miroshnychenko D |
| Citation(s) |
33462489 |
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| Submission date |
Oct 20, 2020 |
| Last update date |
Jan 20, 2021 |
| Contact name |
Daria Miroshnychenko |
| E-mail(s) |
daria.miroshnychenko@moffitt.org
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| Organization name |
Moffitt Cancer Center
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| Department |
Cancer Physiology
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| Lab |
Marusyk Lab
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| Street address |
12902 USF Magnolia Drive
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| City |
TAMPA |
| State/province |
FL |
| ZIP/Postal code |
33612 |
| Country |
USA |
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| Platforms (1) |
| GPL29257 |
Illumina HumanCytoSNP-12v2-1_L1 |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE159681 |
Spontaneous Cell Fusions as a Mechanism of Parasexual Recombination in Tumor Cell Populations |
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| Relations |
| BioProject |
PRJNA670185 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE159680_Illumina2020_Matrix_processed_Miroshnychenko.txt.gz |
69.5 Mb |
(ftp)(http) |
TXT |
| GSE159680_Illumina2020_Matrix_signal_intensities_Miroshnychenko.txt.gz |
50.4 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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