Convergent TP53 loss and evolvability in cancer.
Date
2023-09-25ICR Author
Author
Mansur, MB
Greaves, M
Type
Journal Article
Metadata
Show full item recordAbstract
Cancer cell populations evolve by a stepwise process involving natural selection of the fittest variants within a tissue ecosystem context and as modified by therapy. Genomic scrutiny of patient samples reveals an extraordinary diversity of mutational profiles both between patients with similar cancers and within the cancer cell population of individual patients. Does this signify highly divergent evolutionary trajectories or are there repetitive and predictable patterns?Major evolutionary innovations or adaptations in different species are frequently repeated, or convergent, reflecting both common selective pressures and constraints on optimal solutions. We argue this is true of evolving cancer cells, especially with respect to the TP53 gene. Functional loss variants in TP53 are the most common genetic change in cancer. We discuss the likely microenvironmental selective pressures involved and the profound impact this has on cell fitness, evolvability and probability of subsequent drug resistance.
Collections
Subject
TP53
cancer
convergence
drug resistance
hypoxia
stem cells
Research team
Biol Childhood Leukaemia
Language
eng
Date accepted
2023-08-10
License start date
2023-09-25
Citation
BMC Ecology and Evolution, 2023, 23 (1), pp. 54 -
Publisher
BMC