GENETIC HETEROGENEITY /
TUMOR EVOLUTION

The vast majority of tumors is genetically heterogeneous, meaning that cancers are composed of many different genetic subclones. In recent years, continuous innovation in sequencing techniques has been the main driver to advance our knowledge about genetic heterogeneity in cancers. Unfortunately, little is known about tumor evolution at cell cycle resolution.

Reproduced from Per Uhlén 2017 – Visualizing intratumoral heterogeneity
Real-time imaging of mitotic errors in patient-derived cancer organoids

Organoids are currently the closest representatives of primary human tumors that are compatible with high temporal resolution imaging of cellular events. Our lab has established real-time imaging of patient-derived tumor organoids over periods of days to monitor their evolutionary process – from a single cell to an established tumor population – and examine the level of chromosomal instability in human cancer organoids, as well as the tumor specific tolerance levels to mitotic errors.

Although the research fields of cell biology and genetics are well-established, there is relatively little interaction between both disciplines. Most notably, direct integration between live-cell microscopy with single cell genetics has been challenging to establish. To that end, we are now exploring new strategies, like microfluidics, to combine our established live-cell imaging of tumor organoid growth with single cell genomic analysis. We are interested to decipher the direct genetic consequences of abnormal cellular processes in tumor cells, as well as to study tumor evolution with cell cycle resolution.

  • Drost et al., Nature 2015
  • Bolhaqueiro et al., Nat Genet in press