Naslov
Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes

Autori
Ban, Ivana ; Tomašić, Lucija ; Trakala, Marianna ; Tolić, Iva M. ; Pavin, Nenad

Izvornik
Biophysical Journal (0006-3495) 122 (2023), 4; 632-645

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
karyotype evolution ; tumor karyotype ; aneuploidy ; mathematical model ; theory ; cell proliferation ; apoptosis ; chromosome missegregation ; macro-karyotype

Sažetak
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 increased chromosome missegregation, chromosome gains dominate over losses both in pretumor and tumor tissues, whereas T-cell lymphomas are characterized by gains of chromosomes 14 and 15. However, the quantitative understanding of clonal selection leading to tumor karyotype evolution remains unknown. 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, whereas, 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.

Izvorni jezik
Engleski

Znanstvena područja
Matematika, Fizika, Biologija, Interdisciplinarne prirodne znanosti

POVEZANOST RADA