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Intratumour heterogeneity of p53 expression; causes and consequences.

Authors
  • Xue, Yuezhen1
  • San Luis, Boris1
  • Lane, David P1
  • 1 p53 Laboratory, A*STAR, Singapore, Singapore. , (Singapore)
Type
Published Article
Journal
The Journal of Pathology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Nov 01, 2019
Volume
249
Issue
3
Pages
274–285
Identifiers
DOI: 10.1002/path.5328
PMID: 31322742
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Genomic alterations in different types of cancer have been identified by comprehensive sequencing methodologies, revealing TP53 as the most frequently mutated gene across the majority of human cancer types. Cytotoxic treatments are still major cancer therapy strategies but cancer recurrence due to therapy resistance is a major challenge. Resistant cell populations may be associated with TP53 mutant clones exhibiting abnormal p53 expression patterns in tumours. Given data that levels of mutant p53 influence cancer cell growth and survival, understanding the mechanisms underlying intratumour heterogeneity of p53 can be exploited to design strategies that improve patient survival. The patterns of p53 protein examined by immunohistochemistry of both premalignant and malignant tissues are complex, ranging from intense staining of all tumour cell nuclei to complete absence of staining and with many intermediate phenotypes. Animal models that express only mutant proteins and adoption of international standards for terminology have brought greater clarity to understanding the causes of variation and are at the same time demonstrating the utility of p53 in oncology. In addition to p53 mutation, MDM2 and chaperone activities, gene copy number and TP53 mRNA levels linked to proliferative activity and differentiation are all now established as causes of variation in p53 staining, with clinical implications. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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