Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes

Scientific paper - Original scientific paper

• Author: Ivana Ban
• Author: Lucija Tomašić
• Author: Marianna Trakala
• Author: Iva M. Tolić
• Author: Nenad Pavin
• Author's institution: University of Zagreb; Faculty of Science; (Department of Physics)
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Physics
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Mathematics
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Interdisciplinary Natural Sciences

Abstract (english)

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... More 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. Less

• Keywords (english): karyotype evolution; tumor karyotype; aneuploidy; mathematical model; theory; cell proliferation; apoptosis; chromosome missegregation; macro-karyotype
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review - international
• Publication version: Published version
• Journal title: Biophysical Journal
• Numbering: vol. 122, no. 4, pp. 632-645
• p-ISSN: 0006-3495
• DOI: https://doi.org/10.1016/j.bpj.2023.01.017
• URN:NBN: urn:nbn:hr:217:276672
• Publication: 2023
• Project: Number: 8551580; Title (english): Molecular origins of aneuploidies in healthy and diseased human tissues; Acronym: ANEUPLOIDY; Leader: Iva Marija Tolić; Nenad Pavin; Jurisdiction: eu
• Project: Number: IP-2019-04-5967; Title (croatian): Ravnoteža sila i momenta sila u diobenom vretenu; Title (english): Balance of forces and torques in the mitotic spindle; Acronym: SpindleForceBalance; Leader: Nenad Pavin; Jurisdiction: Croatia; Funding stream: IP
• Project: Number: KK.01.1.1.04.0057; Title (english): Inovative microscopy protocols for interdisciplinary research in biomedicine; Acronym: IPSted; Leader: Iva Marija Tolić; Jurisdiction: eu
• Project: Number: KK.01.1.1.01.0004; Title (english): QuantiXLie Center of Excellence; Acronym: QuantiXLie; Leader: Hrvoje Buljan; Pavle Pandžić; Jurisdiction: eu; Funding stream: European Regional Development Fund - the Competitiveness and Cohesion Operational Programme
• Document URL: https://linkinghub.elsevier.com/retrieve/pii/S0006349523000334
• Type of resource: Text
• Access conditions: Open access
• Public note: Copyright © 2023 Biophysical Society. 2023 Biophysical Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Received 31 August 2022; Accepted 13 January 2023; Available online 18 January 2023; Version of Record 21 February 2023.
• Created on: 2023-08-21 12:33:40