TY - JOUR
T1 - Chromosomal Instability, Selection and Competition
T2 - Factors That Shape the Level of Karyotype Intra-Tumor Heterogeneity
AU - van den Bosch, Tom
AU - Derks, Sarah
AU - Miedema, Daniël M.
N1 - Funding Information: This work was supported by Amsterdam UMC and Oncode Institute. Publisher Copyright: © 2022 by the authors.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Intra-tumor heterogeneity (ITH) is a pan-cancer predictor of survival, with high ITH being correlated to a dismal prognosis. The level of ITH is, hence, a clinically relevant characteristic of a malignancy. ITH of karyotypes is driven by chromosomal instability (CIN). However, not all new karyotypes generated by CIN are viable or competitive, which limits the amount of ITH. Here, we review the cellular processes and ecological properties that determine karyotype ITH. We propose a framework to understand karyotype ITH, in which cells with new karyotypes emerge through CIN, are selected by cell intrinsic and cell extrinsic selective pressures, and propagate through a cancer in competition with other malignant cells. We further discuss how CIN modulates the cell phenotype and immune microenvironment, and the implications this has for the subsequent selection of karyotypes. Together, we aim to provide a comprehensive overview of the biological processes that shape the level of karyotype heterogeneity.
AB - Intra-tumor heterogeneity (ITH) is a pan-cancer predictor of survival, with high ITH being correlated to a dismal prognosis. The level of ITH is, hence, a clinically relevant characteristic of a malignancy. ITH of karyotypes is driven by chromosomal instability (CIN). However, not all new karyotypes generated by CIN are viable or competitive, which limits the amount of ITH. Here, we review the cellular processes and ecological properties that determine karyotype ITH. We propose a framework to understand karyotype ITH, in which cells with new karyotypes emerge through CIN, are selected by cell intrinsic and cell extrinsic selective pressures, and propagate through a cancer in competition with other malignant cells. We further discuss how CIN modulates the cell phenotype and immune microenvironment, and the implications this has for the subsequent selection of karyotypes. Together, we aim to provide a comprehensive overview of the biological processes that shape the level of karyotype heterogeneity.
KW - aneuploidy
KW - chromosomal instability
KW - immunological pressure
KW - intra-tumor heterogeneity
UR - http://www.scopus.com/inward/record.url?scp=85140930107&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers14204986
DO - https://doi.org/10.3390/cancers14204986
M3 - Review article
C2 - 36291770
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 20
M1 - 4986
ER -