Analysis of microsatellite instability in children treated for acute lymphocytic leukemia with elevated HPRT mutant frequencies

Mutagenesis
Heather KendallB A Finette

Abstract

Survival rates of children treated for cancer have increased dramatically over the last 25 years following the development of risk-directed multi-modality treatment protocols. As a result, there is a rapidly growing population of children and young adult cancer survivors in which the long-term genotoxic effects of chemotherapeutic intervention is unknown. We have previously observed that children treated for acute lymphocytic leukemia (ALL) have significantly increased somatic mutant frequencies (Mfs) (30- to 1300-fold higher) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) reporter gene in their non-malignant peripheral T cells compared with children at diagnosis or controls. In order to gain insight into the etiology of the observed dramatic increase in Mfs following antineoplastic therapy, we investigated the prevalence of microsatellite instability (MSI), reflective of a defect in DNA mismatch repair (MMR), in children with ALL at diagnosis, during and after chemotherapy and compared them with healthy age-matched controls. MSI analysis using five microsatellite markers was performed on 167 T cell isolates from 40 healthy children and on 842 T cell isolates from 50 patients treated for ALL. High-frequency MSI (M...Continue Reading

Citations

Mar 11, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·H H KuoT C Wang
Jan 24, 2008·British Journal of Cancer·R J C SlebosW G Yarbrough

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