Revisiting Clonal Evolution Through the Light of Retrotransposons

The clonal evolution model provides a framework for understanding the evolution of cancer cells. According to this model, cancer cells accumulate genetic mutations over time, and these mutations are passed down to their descendants, leading to genetic diversity within the tumor. Some of these mutations confer selective advantages, causing certain lineages of cancer cells (clones) to dominate and expand. However, this model is rooted in certain conceptual assumptions, which we propose to revisit by considering the potential involvement of retrotransposons in cancer initiation and progression. In recent years, it has become evident that transposable elements, particularly retrotransposons, play a significant role in driving cancer transformation and progression. We first review how current knowledge about retrotransposon activity aligns with the clonal evolution model by highlighting its ability to modulate cancer cell fitness. We then take a forward-looking perspective to explore additional ways retrotransposons may also influence clonal dynamics beyond the current model.