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

Abstract

Recent studies have brought to the forefront the importance of somatic mutations during human fetal development and malignant transformation in children, specifically leukemia. Therefore, a better understanding of the frequency and mutational spectrum of spontaneous in utero mutations is essential for understanding the genetic mechanisms associated with pediatric malignancies. 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 phosphoribosyltransferase (HPRT) reporter gene mutational spectra analysis for 60 T-cell mutant isolates from the umbilical cord blood of preterm newborns to gain insight into background mutational events during the late stages of fetal development. Logistic regression analyses showed a significant increase in HPRT deletions mediated by V(D)J recombinase in preterm newborns compared with full-term newborns (P = 0.009). A comparative analysis of deletion mutations also revealed that V(D)J recombinase-mediated HPRT deletions increased with decreasing gestational age (P = 0.012) and were significantly higher in females than males of the same developmental status (P = 0.031). Developmental and gender-specific differences in HPRT deletions mediated by V(D)J recombinase provide insight into the gender-specific differences seen in infant leukemia.

• Authors: M Yoshioka, J P O'Neill, P M Vacek, B A Finette
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 8 Pg. 3432-8 (Apr 15 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11309304 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hypoxanthine Phosphoribosyltransferase
• DNA Nucleotidyltransferases
• VDJ Recombinases

Topics

• Base Sequence
• Chromosome Breakage
• DNA Mutational Analysis
• DNA Nucleotidyltransferases (genetics)
• Female
• Fetal Blood (cytology, enzymology, physiology)
• Gene Deletion
• Gestational Age
• Humans
• Hypoxanthine Phosphoribosyltransferase (genetics)
• Infant, Newborn
• Infant, Premature (blood, physiology)
• Logistic Models
• Male
• Molecular Sequence Data
• Mutation
• Sex Factors
• T-Lymphocytes (enzymology, physiology)
• VDJ Recombinases