Establishing the Link between X-Chromosome Aberrations and TP53 Status, with Breast Cancer Patient Outcomes.
Cells
; 12(18)2023 09 11.
Article
em En
| MEDLINE
| ID: mdl-37759468
ABSTRACT
Ubiquitous to normal female human somatic cells, X-chromosome inactivation (XCI) tightly regulates the transcriptional silencing of a single X chromosome from each pair. Some genes escape XCI, including crucial tumour suppressors. Cancer susceptibility can be influenced by the variability in the genes that escape XCI. The mechanisms of XCI dysregulation remain poorly understood in complex diseases, including cancer. Using publicly available breast cancer next-generation sequencing data, we show that the status of the major tumour suppressor TP53 from Chromosome 17 is highly associated with the genomic integrity of the inactive X (Xi) and the active X (Xa) chromosomes. Our quantification of XCI and XCI escape demonstrates that aberrant XCI is linked to poor survival. We derived prognostic gene expression signatures associated with either large deletions of Xi; large amplifications of Xa; or abnormal X-methylation. Our findings expose a novel insight into female cancer risks, beyond those associated with the standard molecular subtypes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Cells
Ano de publicação:
2023
Tipo de documento:
Article