New germline mutations in the hypervariable minisatellite CEB1 in the parents of children with leukaemia

B. G. Davies, A. Hussain, S. M. Ring, J. M. Birch, T. O B Eden, M. Reeves, Y. E. Dubrova, G. M. Taylor

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Gardner and co-workers advanced the hypothesis that the Seascale leukaemia cluster could have been caused by new mutations in germ cells, induced by paternal preconceptional irradiation (PPI) exposure at the Sellafield nuclear installation. Since evidence has shown that PPI can increase the de novo germline mutation rate in hypervariable minisatellite loci, we investigated the hypothesis that sporadic childhood leukaemia might be associated with an increased parental germline minisatellite mutation rate. To test this hypothesis, we compared de novo germline mutation rates in the hypervariable minisatellite locus, CEB1, in family trios (both parents and their child) of children with leukaemia (n=135) compared with unaffected control families (n=124). The majority of case and control germline mutations were paternal (94%); the mean paternal germline mutation rates of children with leukaemia (0.083) and control children (0.156) were not significantly different (odds ratio, 95% confidence interval: 0.50, 0.23-1.08; P=0.11). There were no significant differences in case and control parental allele sizes, case and control germline mutation progenitor allele sizes (2.74 vs 2.54 kb; P=0.56), case and control mutant allele sizes (2.71 vs 2.67 kb; P=0.90), mutant allele size changes (0.13 vs 0.26 kb; P=0.10), or mutational spectra. Within the limitation of the number of families available for study, we conclude that childhood leukaemia is unlikely to be associated with increased germline minisatellite instability. © 2007 Cancer Research UK.
    Original languageEnglish
    Pages (from-to)1265-1271
    Number of pages6
    JournalBritish Journal of Cancer
    Volume96
    Issue number8
    DOIs
    Publication statusPublished - 23 Apr 2007

    Keywords

    • Childhood leukaemia
    • Germline
    • Minisatellite
    • Mutation

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