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Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns. | LitMetric

AI Article Synopsis

  • The study focuses on how genetic diversity in tumors arises, particularly the formation and spread of karyotype alterations in human tumors at a single-cell level.
  • Researchers developed a method called 3D Live-Seq that combines live imaging of tumor organoids and whole-genome sequencing to track changes in tumor cells over generations.
  • Findings show that karyotype changes occur rapidly and can either happen gradually through multiple cell divisions or emerge suddenly from a single division, highlighting the complex evolution of tumor genomes.

Article Abstract

Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq-a protocol that integrates live-cell imaging of tumor organoid outgrowth and whole-genome sequencing of each imaged cell to reconstruct evolving tumor cell karyotypes across consecutive cell generations. Using patient-derived colorectal cancer organoids and fresh tumor biopsies, we demonstrate that karyotype alterations of varying complexity are prevalent and can arise within a few cell generations. Sub-chromosomal acentric fragments were prone to replication and collective missegregation across consecutive cell divisions. In contrast, gross genome-wide karyotype alterations were generated in a single erroneous cell division, providing support that aneuploid tumor genomes can evolve via punctuated evolution. Mapping the temporal dynamics and patterns of karyotype diversification in cancer enables reconstructions of evolutionary paths to malignant fitness.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346364PMC
http://dx.doi.org/10.1038/s41588-021-00891-2DOI Listing

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