Regensburg 2022 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 23: Evolution
BP 23.2: Vortrag
Donnerstag, 8. September 2022, 10:15–10:30, H13
Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes — •Lucija Tomašić1, Ivana Ban1, Marianna Trakala2, Iva Tolić3, and Nenad Pavin1 — 1Department of Physics, Faculty of Science, University of Zagreb, Croatia — 2David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA — 3Division of Molecular Biology, Ruder Bošković Institute, Croatia
Most tumors have abnormal karyotypes, which arise from mistakes during mitotic division of healthy euploid cells and evolve through numerous complex mechanisms. In a recent mouse model with high levels of chromosome missegregation, chromosome gains dominate over losses both in pretumor and tumor tissues, whereas tumors are characterized by gains of chromosomes 14 and 15. However, the mechanisms driving clonal selection leading to tumor karyotype evolution remain unclear. Here we show, by introducing a mathematical model based on a concept of a macro-karyotype, that tumor karyotypes can be explained by proliferation-driven evolution of aneuploid cells. In pretumor cells, increased apoptosis and slower proliferation of cells with monosomies lead to predominant chromosome gains over losses. Tumor karyotypes with gain of one chromosome can be explained by karyotype-dependent proliferation, while for those with two chromosomes an interplay with karyotype-dependent apoptosis is an additional possible pathway. Thus, evolution of tumor-specific karyotypes requires proliferative advantage of specific aneuploid karyotypes.