A prospective study of hprt mutant and mutation frequencies in treated cancer patients

We previously reported that some Hodgkin's disease patients had elevated hprt mutant frequencies in peripheral blood lymphocytes long after cessation of therapy. To determine if these elevations in mutant frequency represent true persistently elevated mutation frequencies, we recruited for a prospective study six previously treated Hodgkin's disease patients and five patients who had been treated for squamous cell carcinoma of the head and neck. These individuals were studied several times over a 6-7-month period. The results confirmed that a subset of patients have persistently high mutant frequencies when compared to 71 previously studied controls. The present study was designed to determine if the elevated mutant frequencies of treated patients represented independent mutations or resulted from the in vivo expansion of single mutant cells. We used the polymerase chain reaction to examine DNA single-strand conformation polymorphisms at the T-cell receptor gamma locus of individual mutant clones. This analysis showed that at any given time 20.1% of the mutants from Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma patients consisted of siblings, identified as having identical polymerase chain reaction/single-stranded conformation polymorphism patterns. The remaining mutants had unique polymerase chain reaction/single-stranded conformation polymorphism patterns and therefore can be presumed to have arisen from independent mutational events. Particular sibling mutants generally did not persist over time. However, one patient had one mutant clone which persisted but slowly decreased in prevalence over a 7-month sampling period. The data demonstrate that treatments for cancer result in persistently elevated mutation frequencies at the hprt locus in some, but not all, patients.(ABSTRACT TRUNCATED AT 250 WORDS)