Berlin 2024 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 29: Statistical Physics of Biological Systems II (joint session BP/DY)
BP 29.8: Vortrag
Donnerstag, 21. März 2024, 11:30–11:45, H 1028
Exploring tumor karyotype evolution using the Macro-Karyotype concept — •Lucija Tomašić1, Thomas van Ravesteyn2,3, Geert J. P. L. Kops2,3, and Nenad Pavin1 — 1Faculty of Science, University of Zagreb, Croatia — 2Hubrecht Institute and University Medical Centre Utrecht, Utrecht, The Netherlands — 3Oncode Institute, Utrecht, The Netherlands
Most tumors exhibit abnormal chromosome content (karyotype) resulting from errors in mitotic division. While tumors tend to manifest diverse karyotype aberrations, typically with gains of specific chromosomes, understanding the dynamics leading to these configurations is challenging due to the dimensionality of the karyotype space. To address this complexity, we introduce the 'Macro-Karyotype' concept,a novel framework for comprehensively exploring tumor chromosomal evolution. Combining in vitro organoid evolution with mathematical modeling, our study demonstrates that premalignant human organoids spontaneously undergo chromosome copy number alterations related to cancer. A gradual gain of specific chromosomes over time is observed, propelled by the enhanced fitness of these karyotypes. Additionally, some karyotypes undergo dramatic changes through whole-genome duplication and multipolar divisions, followed by normalization over time through the selection of karyotypes with lower mitotic error rates. Our findings uncover the selection of homogeneous karyotypes driven by cellular fitness, significantly constraining the available karyotype space. Our study deepens understanding of tumor karyotype evolution and informs factors influencing cancer related chromosomal changes.
Keywords: Tumor; Cancer; Aneuploidy; Single-cell sequencing; Karyotype