Cool new paper from @AndriyMarusyk and colleagues: Cancer cells can have sex, and it makes them stronger. https://www.nature.com/articles/s41559-020-01367-y

Cancer cells are generally thought of as “asexual” - they spread by clonal propagation. However, if you’ve ever spent any time looking at cancer cells in a petri dish, you know that they form lots of funky structures that don’t exactly look like single cells.

Andriy and colleagues set out to investigate whether different cancer cells could actually undergo cell-cell fusion - which could allow those cells to recombine their genetic material.

By mixing cells labeled with different fluorophores or drug resistance markers, they demonstrated that bona fide cell fusion was in fact occurring between a small fraction of cells!

They characterized the malignant properties of these cells, and discovered that the fused cells exhibited increased proliferation and invasive behavior. This suggests that the fusion event increased their fitness.

Then, they explored what was happening at the genetic level. The fused cells were initially polyploid, as you’d expect. However, over time, the cells underwent reductive mitoses, shedding extra chromosomes and reverting to a lower ploidy.

When they looked at SNPs that could distinguish the parental cell lines, they found that SNPs from both parents were inherited on the same chromosomes. This suggested that the chromosomes were undergoing recombination, leading to an unequal inheritance of parental alleles!

Finally, using mathematical modeling, the suggest that these fusion and parasexual recombination events could help fitness-promoting alleles spread throughout a cell population:

Up next: can this fusion/recombination/reductive mitosis process be documented in actual tumors? Also, I think that long-read sequencing of these recombination events would be very informative.

Overall, I think that these results underscore just how weird cancer genetics is. Even with petabytes of tumor sequencing data, there’s still a lot more left to uncover!