Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network - Sorbonne Université Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2019

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

Résumé

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.
Fichier principal
Vignette du fichier
s41467-019-13266-3.pdf (1.24 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-02406712 , version 1 (12-12-2019)

Identifiants

Citer

Sue Haupt, Franco Caramia, Alan Herschtal, Thierry Soussi, Guillermina Lozano, et al.. Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network. Nature Communications, 2019, 10, pp.5385. ⟨10.1038/s41467-019-13266-3⟩. ⟨hal-02406712⟩
28 Consultations
50 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More