Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network
Details
Publication Year 2019-11-26, Volume 10, Issue #1, Page 5385
Journal Title
Nature Communications
Publication Type
Journal Article
Abstract
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.
Publisher
NPG
WEHI Research Division(s)
Bioinformatics
PubMed ID
31772231
Open Access at Publisher's Site
https://doi.org/10.1038/s41467-019-13266-3
NHMRC Grants
NHMRC/1054618
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-12-05 01:26:18
Last Modified: 2019-12-05 01:43:52
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