Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network
- Haupt, S; Caramia, F; Herschtal, A; Soussi, T; Lozano, G; Chen, H; Liang, H; Speed, TP; Haupt, Y;
Publication Year 2019-11-26, Volume 10, Issue #1, Page 5385
- Journal Title
- Nature Communications
- Publication Type
- Journal 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.
- WEHI Research Division(s)
- PubMed ID
- Publisher's Version
- Open Access at Publisher's Site
- NHMRC Grants
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-12-05 01:26:18Last Modified: 2019-12-05 01:43:52