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Chemosensitivity profiles identify polymorphisms in the p53 network genes 14-3-3tau and CD44 that affect sarcoma

Alexei Vazquez1, Lukasz F Grochola, Elisabeth E Bond

  • 1The Institute for Advanced Study, Princeton, New Jersey, USA.

Cancer Research
|December 10, 2009
PubMed

Insights

Genetic variations in p53 stress response genes, specifically in 14-3-3tau and CD44, impact cancer drug response. These single nucleotide polymorphisms (SNPs) may predict patient survival and diagnosis age in soft-tissue sarcoma.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • The p53 regulatory network is crucial for cellular stress responses, including apoptosis and cell cycle arrest, which are vital in cancer prevention and therapy.
  • Functional genetic variants within this network can influence cancer risk and therapeutic outcomes, but remain largely uncharacterized.

Purpose of the Study:

  • To identify single nucleotide polymorphisms (SNPs) in p53 stress response genes associated with differential cellular responses to chemotherapeutic agents.
  • To evaluate the clinical relevance of identified SNPs in soft-tissue sarcoma patients regarding survival and age of diagnosis.

Main Methods:

  • Utilized the NCI60 human tumor cell line drug screen to analyze SNPs in 142 p53 stress response genes.
  • Correlated allelic differences in identified SNPs with cellular sensitivity to a broad spectrum of cytotoxic drugs.
  • Examined the association of significant SNPs with overall survival and age of diagnosis in a cohort of soft-tissue sarcoma patients.

Main Results:

  • Identified 7 SNPs demonstrating significant allelic differences in cellular responses to chemotherapeutics.
  • SNPs in 14-3-3tau (rs6734469) and CD44 (rs187115) showed the most pronounced effects on drug response.
  • In soft-tissue sarcoma patients, specific alleles correlated with poorer overall survival and earlier age of diagnosis.

Conclusions:

  • Genetic variants in 14-3-3tau and CD44 serve as potential biomarkers for predicting chemotherapeutic response.
  • These findings may enhance treatment strategies and prognostic assessments for soft-tissue sarcoma patients.

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