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Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

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Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...

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Rationale for Testing TP53 Mutations in Thyroid Cancer-Original Data and Meta-Analysis.

Katarzyna Lacka1, Adam Maciejewski1, Piotr Tyburski2

  • 1Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland.

International Journal of Molecular Sciences
|February 13, 2025
PubMed
Summary
This summary is machine-generated.

TP53 mutations are common in anaplastic thyroid cancer (ATC) but rare in differentiated thyroid cancer (DTC). p53 overexpression is a marker in both DTC and ATC, warranting further study for prognostic value in DTC.

Keywords:
immunohistochemistrymeta-analysismutationp53thyroid cancer

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The p53 protein is a crucial tumor suppressor involved in tumorigenesis.
  • TP53 mutations are infrequent in differentiated thyroid cancer (DTC) but prevalent in anaplastic thyroid cancer (ATC).

Purpose of the Study:

  • To investigate the prognostic significance of TP53 mutations and surrogate markers (p53 expression, p53-Abs) in thyroid cancer.
  • To differentiate the role of TP53 alterations in DTC versus ATC.

Main Methods:

  • Original analysis of TP53 mutations via SSSP and direct sequencing in DTC, ATC, and control groups.
  • Immunohistochemical assessment of p53 expression in tissue samples.
  • Meta-analysis of 14 studies on TP53 mutations and p53 expression in thyroid cancer.

Main Results:

  • TP53 mutations were found in all ATC cases and 6.67% of DTC cases.
  • p53 overexpression was significantly higher in both DTC (26.67%) and ATC compared to controls.
  • Meta-analysis confirmed TP53 mutations are more frequent in ATC than controls (OR 8.95, p=0.02), but not significantly in DTC vs. controls (OR 1.87, p=0.33).
  • p53 overexpression (OR 7.99 for DTC, OR 64.37 for ATC) and serum p53-Abs positivity (OR 2.07 for PTC) were significantly elevated versus controls.

Conclusions:

  • TP53 mutations are key events in ATC development.
  • While p53 overexpression and serum p53-Abs are elevated in DTC, their prognostic value requires further investigation through prospective studies.