Gestational age and gender-specific in utero V(D)J recombinase-mediated deletions

Recent studies have brought to the forefront the importance of somatic muta tions during human fetal development and malignant transformation in childr en, specifically leukemia, Therefore, a better understanding of the frequen cy and mutational spectrum of spontaneous in utero mutations is essential f or understanding the genetic mechanisms associated with pediatric malignanc ies. Previously we reported that the frequency of somatic mutations during the late stages of fetal development was dependent on both gestational age and gender. Here we present the hypoxanthine-guanine phosphoribosyltransfer ase (HPRT) reporter gene mutational spectra analysis for 60 T-cell mutant i solates from the umbilical cord blood of preterm newborns to gain insight i nto background mutational events during the tate stages of fetal developmen t. Logistic regression analyses shoved a significant increase in HPRT delet ions mediated by V(D)J recombinase in preterm newborns compared with full-t erm new-borns (P = 0.009). A comparative analysis of deletion mutations als o revealed that Y(D)J recombinase-mediated HPRT deletions increased with de creasing gestational age (P = 0.012) and were significantly higher in femal es than males of the same developmental status (P = 0.031). Developmental a nd gender-specific differences in HPRT deletions mediated by Y(D)J recombin ase provide insight into the gender-specific differences seen in infant leu kemia.