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Related Experiment Videos

Mutagenesis after cancer therapy

K T Kelsey1, M Caggana, P M Mauch

  • 1Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.

Environmental Health Perspectives
|October 1, 1993
PubMed
Summary

Cancer therapies can cause persistently high mutation frequencies in some patients, as measured by elevated hypoxanthine-guanine phosphoribosyltransferase (hprt) mutant frequencies. This study investigated if these mutations were from new independent events or cell expansion.

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Elevated hypoxanthine-guanine phosphoribosyltransferase (hprt) mutant frequencies observed in some Hodgkin's disease (HD) and breast cancer patients post-therapy.
  • These patients sometimes develop second therapy-related malignancies, raising concerns about persistent mutations.

Purpose of the Study:

  • To determine if elevated hprt mutant frequencies in treated cancer patients represent true, persistent mutations.
  • To investigate whether these elevated frequencies result from independent mutations or in vivo expansion of single mutant cells.

Main Methods:

  • Prospective study of six previously treated HD patients and five patients treated for head and neck squamous cell carcinoma.
  • Serial blood sample analysis over 6-7 months to measure hprt mutant frequencies.

Related Experiment Videos

  • Polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis at the T-cell receptor-gamma locus to identify sibling mutant clones.

    • Main Results:

    • A subset of patients exhibited persistently high hprt mutant frequencies compared to controls.
    • Sibling mutants, indicating expansion from a single cell, were found in 20.1% of HD patients and 17.5% of squamous cell carcinoma patients.
    • Sibling mutants generally did not persist, though one patient showed a slowly decreasing persistent mutant clone.

    Conclusions:

    • Cancer treatments can lead to persistently elevated hprt mutation frequencies in some individuals.
    • The study distinguished between independent mutations and clonal expansion, with evidence of both occurring post-therapy.
    • Findings underscore the importance of monitoring mutation frequencies in cancer survivors.