Establishing the Link between X-Chromosome Aberrations and <i>TP53</i> Status, with Breast Cancer Patient Outcomes
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 gen...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/18/2245 |
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| author | Franco Caramia Terence P. Speed Hui Shen Ygal Haupt Sue Haupt |
| author_facet | Franco Caramia Terence P. Speed Hui Shen Ygal Haupt Sue Haupt |
| author_sort | Franco Caramia |
| collection | DOAJ |
| description | 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 <i>TP53</i> 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. |
| first_indexed | 2024-03-10T22:56:31Z |
| format | Article |
| id | doaj.art-a783c30d86904abfac32b7464c48a57f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T22:56:31Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a783c30d86904abfac32b7464c48a57f2023-11-19T09:59:21ZengMDPI AGCells2073-44092023-09-011218224510.3390/cells12182245Establishing the Link between X-Chromosome Aberrations and <i>TP53</i> Status, with Breast Cancer Patient OutcomesFranco Caramia0Terence P. Speed1Hui Shen2Ygal Haupt3Sue Haupt4Peter MacCallum Cancer Centre, Melbourne, VIC 3000, AustraliaWalter and Eliza Hall Institute for Medical Research, Parkville, VIC 3052, AustraliaVan Andel Institute, Grand Rapids, MI 49503, USAPeter MacCallum Cancer Centre, Melbourne, VIC 3000, AustraliaPeter MacCallum Cancer Centre, Melbourne, VIC 3000, AustraliaUbiquitous 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 <i>TP53</i> 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.https://www.mdpi.com/2073-4409/12/18/2245X chromosomeXCIbreast cancerTP53TCGAMETABRIC |
| spellingShingle | Franco Caramia Terence P. Speed Hui Shen Ygal Haupt Sue Haupt Establishing the Link between X-Chromosome Aberrations and <i>TP53</i> Status, with Breast Cancer Patient Outcomes Cells X chromosome XCI breast cancer TP53 TCGA METABRIC |
| title | Establishing the Link between X-Chromosome Aberrations and <i>TP53</i> Status, with Breast Cancer Patient Outcomes |
| title_full | Establishing the Link between X-Chromosome Aberrations and <i>TP53</i> Status, with Breast Cancer Patient Outcomes |
| title_fullStr | Establishing the Link between X-Chromosome Aberrations and <i>TP53</i> Status, with Breast Cancer Patient Outcomes |
| title_full_unstemmed | Establishing the Link between X-Chromosome Aberrations and <i>TP53</i> Status, with Breast Cancer Patient Outcomes |
| title_short | Establishing the Link between X-Chromosome Aberrations and <i>TP53</i> Status, with Breast Cancer Patient Outcomes |
| title_sort | establishing the link between x chromosome aberrations and i tp53 i status with breast cancer patient outcomes |
| topic | X chromosome XCI breast cancer TP53 TCGA METABRIC |
| url | https://www.mdpi.com/2073-4409/12/18/2245 |
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