Journal article

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

Nature Communications | NATURE PUBLISHING GROUP | Published : 2019

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..

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Grants

Awarded by NHMRC


Awarded by NBCF


Funding Acknowledgements

Prof Arnie Levine for his helpful comments and suggestions. Simon Keam for assistance with the graphic software package. Jason Li and Richard Tothill for bioinformatics advice. The Haupt lab acknowledges funding from the following sources: NHMRC (1123057), NBCF (IN-16-042), Sister Institution Network Fund (SINF): MD Anderson Peter Mac, and the Peter MacCallum Foundation. T.P.S. acknowledges funding from NHMRC Program Grant 1054618.