Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes.
Biophys J
; 122(4): 632-645, 2023 02 21.
Article
em En
| MEDLINE
| ID: mdl-36654508
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aneuploidia
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Croácia