Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network
AuthorHaupt, S; Caramia, F; Herschtal, A; Soussi, T; Lozano, G; Chen, H; Liang, H; Speed, TP; Haupt, Y
Source TitleNature Communications
PublisherNATURE PUBLISHING GROUP
Sir Peter MacCallum Department of Oncology
School of Mathematics and Statistics
Document TypeJournal Article
CitationsHaupt, S., Caramia, F., Herschtal, A., Soussi, T., Lozano, G., Chen, H., Liang, H., Speed, T. P. & Haupt, Y. (2019). Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network. NATURE COMMUNICATIONS, 10 (1), https://doi.org/10.1038/s41467-019-13266-3.
Access StatusOpen Access
NHMRC Grant codeNHMRC/1123057
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.
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