Cited by 94Cancer-related Molecular PathwaysCancer Genomics and DiagnosticsGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

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

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Haupt, Sue, Caramia, Franco, Herschtal, Alan, Soussi, Thierry, Lozano, Guillermina, Chen, Hu, Liang, Han, Speed, Terence P. +1 more·2019·Nature Communications

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.

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Authors
Haupt, S., Caramia, F., Herschtal, A., Soussi, T., Lozano, G., Chen, H., Liang, H., Speed, T. P., & Haupt, Y.
Affiliations
  • The University of Melbourne (AU)
  • Inserm (FR)
  • The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Haupt, Sue
Venue
Nature Communications
Published
2019-11-26
Volume
10
Issue
1
Pages
5385-5385
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2991018046
Cited by
94
References
85
Citations by year
2026: 8 · 2025: 12 · 2024: 18 · 2023: 15 · 2022: 21 · 2021: 13 · 2020: 5 · 2017: 1
FWCI
4.07
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Breast Cancer Foundation (IN-16-042)
  • Peter MacCallum Foundation (1123057)
  • University of Texas MD Anderson Cancer Center
  • National Health and Medical Research Council (1054618, 1123057)
  • National Cancer Institute (P30CA016672)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Keywords
sex differences in cancer, TP53 mutation, p53, X chromosome, X-linked genes, tumor suppressor, cancer survival, sex-biased gene expression
MeSH terms
Female, Humans, Male, Neoplasms, Sex Factors, United States, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, SEER Program, Chromosomes, Human, X, Genes, X-Linked, Exome, Mutation Rate, Protein Interaction Maps

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