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Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network
The disproportionately high prevalence of male cancer is poorly understood. We tested for sex-disparity in the functional integrity of the major tumor suppressor p53 in sporadic cancers. Our bioinformatics analyses expose three novel levels of p53 impact on sex-disparity in 12 non-reproductive cance...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879765/ https://www.ncbi.nlm.nih.gov/pubmed/31772231 http://dx.doi.org/10.1038/s41467-019-13266-3 |
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author | Haupt, Sue Caramia, Franco Herschtal, Alan Soussi, Thierry Lozano, Guillermina Chen, Hu Liang, Han Speed, Terence P. Haupt, Ygal |
author_facet | Haupt, Sue Caramia, Franco Herschtal, Alan Soussi, Thierry Lozano, Guillermina Chen, Hu Liang, Han Speed, Terence P. Haupt, Ygal |
author_sort | Haupt, Sue |
collection | PubMed |
description | The disproportionately high prevalence of male cancer is poorly understood. We tested for sex-disparity in the functional integrity of the major tumor suppressor p53 in sporadic cancers. Our bioinformatics analyses expose three novel levels of p53 impact on sex-disparity in 12 non-reproductive cancer types. First, TP53 mutation is more frequent in these cancers among US males than females, with poorest survival correlating with its mutation. Second, numerous X-linked genes are associated with p53, including vital genomic regulators. Males are at unique risk from alterations of their single copies of these genes. High expression of X-linked negative regulators of p53 in wild-type TP53 cancers corresponds with reduced survival. Third, females exhibit an exceptional incidence of non-expressed mutations among p53-associated X-linked genes. Our data indicate that poor survival in males is contributed by high frequencies of TP53 mutations and an inability to shield against deregulated X-linked genes that engage in p53 networks. |
format | Online Article Text |
id | pubmed-6879765 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68797652019-11-29 Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network Haupt, Sue Caramia, Franco Herschtal, Alan Soussi, Thierry Lozano, Guillermina Chen, Hu Liang, Han Speed, Terence P. Haupt, Ygal Nat Commun Article The disproportionately high prevalence of male cancer is poorly understood. We tested for sex-disparity in the functional integrity of the major tumor suppressor p53 in sporadic cancers. Our bioinformatics analyses expose three novel levels of p53 impact on sex-disparity in 12 non-reproductive cancer types. First, TP53 mutation is more frequent in these cancers among US males than females, with poorest survival correlating with its mutation. Second, numerous X-linked genes are associated with p53, including vital genomic regulators. Males are at unique risk from alterations of their single copies of these genes. High expression of X-linked negative regulators of p53 in wild-type TP53 cancers corresponds with reduced survival. Third, females exhibit an exceptional incidence of non-expressed mutations among p53-associated X-linked genes. Our data indicate that poor survival in males is contributed by high frequencies of TP53 mutations and an inability to shield against deregulated X-linked genes that engage in p53 networks. Nature Publishing Group UK 2019-11-26 /pmc/articles/PMC6879765/ /pubmed/31772231 http://dx.doi.org/10.1038/s41467-019-13266-3 Text en © Crown 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Haupt, Sue Caramia, Franco Herschtal, Alan Soussi, Thierry Lozano, Guillermina Chen, Hu Liang, Han Speed, Terence P. Haupt, Ygal Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network |
title | Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network |
title_full | Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network |
title_fullStr | Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network |
title_full_unstemmed | Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network |
title_short | Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network |
title_sort | identification of cancer sex-disparity in the functional integrity of p53 and its x chromosome network |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879765/ https://www.ncbi.nlm.nih.gov/pubmed/31772231 http://dx.doi.org/10.1038/s41467-019-13266-3 |
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