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Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns.
- Source :
-
Nature genetics [Nat Genet] 2021 Aug; Vol. 53 (8), pp. 1187-1195. Date of Electronic Publication: 2021 Jul 01. - Publication Year :
- 2021
-
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.<br /> (© 2021. The Author(s).)
- Subjects :
- Cell Proliferation genetics
Chromatin genetics
Chromosomes, Human
Gene Dosage
Humans
Karyotype
Karyotyping
Microscopy, Confocal
Mitosis
Organoids growth & development
Organoids pathology
Spindle Apparatus genetics
Colorectal Neoplasms genetics
Colorectal Neoplasms pathology
Single-Cell Analysis methods
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1718
- Volume :
- 53
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 34211178
- Full Text :
- https://doi.org/10.1038/s41588-021-00891-2