Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes

Ban, Ivana; Tomašić, Lucija; Trakala, Marianna; Tolić, Iva M.; Pavin, Nenad (2023) Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes. Biophysical Journal, 122 (4). pp. 632-645. ISSN 0006-3495

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	karyotype evolution ; tumor karyotype ; aneuploidy ; mathematical model ; theory ; cell proliferation ; apoptosis ; chromosome missegregation ; macro-karyotype
Subjects:	NATURAL SCIENCES > Mathematics NATURAL SCIENCES > Biology NATURAL SCIENCES > Interdisciplinary Natural Sciences
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Molekularno podrijetlo aneuploidija u zdravim i bolesnim ljudskim tkivima Tolić, Iva; Pavin, Nenad 855158 EK Ravnoteža sila i momenta sila u diobenom vretenu Pavin, Nenad IP-2019-04-5967 HRZZ Inovativni protokoli mikroskopije za interdisciplinarna istraživanja u biomedicini Tolić, Iva Marija KK.01.1.1.04.0057 EK Provedba vrhunskih istraživanja u sklopu Znanstvenog centra izvrsnosti za kvantne i kompleksne sustave te reprezentacije Liejevih algebri Buljan, Hrvoje; Pandžić, Pavle; Tuček, Vit; Marketin, Tomislav KK.01.1.1.01.0004 EK
Depositing User:	Iva Tolić
Date Deposited:	16 Jun 2023 10:25
URI:	http://fulir.irb.hr/id/eprint/8032
DOI:	10.1016/j.bpj.2023.01.017

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