Establishing the Link between X-Chromosome Aberrations and TP53 Status, with Breast Cancer Patient Outcomes
- Author(s)
- Caramia, F; Speed, TP; Shen, H; Haupt, Y; Haupt, S;
- Details
- Publication Year 2023-09-11,Volume 12,Issue #18,Page 2245
- Journal Title
- Cells
- 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.
- Publisher
- MDPI
- Keywords
- Humans; Female; *Breast Neoplasms/genetics; Chromosome Aberrations; Genomics; High-Throughput Nucleotide Sequencing; Protein Processing, Post-Translational; Tumor Suppressor Protein p53/genetics; Metabric; Tcga; Tp53; X chromosome; Xci; breast cancer
- Research Division(s)
- Bioinformatics
- PubMed ID
- 37759468
- Publisher's Version
- https://doi.org/10.3390/cells12182245
- Open Access at Publisher's Site
https://doi.org/10.3390/cells12182245- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-11-15 10:47:37
Last Modified: 2023-11-15 10:51:32