Mutation-selection balance and compensatory mechanisms in tumour evolution.
Nat Rev Genet
; 22(4): 251-262, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33257848
ABSTRACT
Intratumour heterogeneity and phenotypic plasticity, sustained by a range of somatic aberrations, as well as epigenetic and metabolic adaptations, are the principal mechanisms that enable cancers to resist treatment and survive under environmental stress. A comprehensive picture of the interplay between different somatic aberrations, from point mutations to whole-genome duplications, in tumour initiation and progression is lacking. We posit that different genomic aberrations generally exhibit a temporal order, shaped by a balance between the levels of mutations and selective pressures. Repeat instability emerges first, followed by larger aberrations, with compensatory effects leading to robust tumour fitness maintained throughout the tumour progression. A better understanding of the interplay between genetic aberrations, the microenvironment, and epigenetic and metabolic cellular states is essential for early detection and prevention of cancer as well as development of efficient therapeutic strategies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adaptação Fisiológica
/
Epigênese Genética
/
Microambiente Tumoral
/
Neoplasias
Tipo de estudo:
Screening_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article