Mutagenesis after cancer therapy.
A subset of Hodgkin's disease (HD) and breast cancer patients have been reported to have elevated hprt mutant frequencies in peripheral blood lymphocytes after cessation of therapy. A subset of these patients are also known to develop second therapy-related malignancies. Therefore, it is clearly important to determine if these elevations in mutant frequency represent true, persistently elevated mutation frequencies. As a follow-up to our study of patients previously treated for HD, we recruited for a prospective study six previously treated HD 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 months. The results confirmed that a subset of patients have persistently high mutant frequencies when compared to 71 previously studied controls. The 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 20.1% of the mutants from Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma patients were siblings. The sibling mutants generally did not persist over time. However, one patient had one mutant clone that 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)
Kelsey
K T
KT
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
Caggana
M
M
Mauch
P M
PM
Coleman
C N
CN
Clark
J R
JR
Liber
H L
HL
D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D006689:Hodgkin Disease / Q000235:genetics / Q000628:therapy*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016296:Mutagenesis; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics*; D011446:Prospective Studies