Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network

Sue Haupt, Franco Caramia, Alan Herschtal, Thierry Soussi, Guillermina Lozano, Hu Chen, Han Liang, Terence P. Speed, Ygal Haupt

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48 Citations (Scopus)


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.

Original languageEnglish
Article number5385
Number of pages12
JournalNature Communications
Issue number1
Publication statusPublished - 26 Nov 2019

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