Emergence of Genetic Instability in Children Treated for Leukemia
- 21 April 2000
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 288 (5465) , 514-517
- https://doi.org/10.1126/science.288.5465.514
Abstract
T cells from patients who had received chemotherapy for B-lineage acute lymphocytic leukemia were studied to determine whether genetic instability, a principal characteristic of cancer cells, can also occur in nonmalignant cells. Consistent with expectations for a genetic instability phenotype, multiple mutations were detected in the hypoxanthine-guanine phosphoribosyltransferase ( HPRT ) reporter gene in independently isolated mutant T cells expressing identical rearranged T cell receptor β (TCRβ) gene hypervariable regions. These results indicate that cancer treatment can lead to genetic instability in nonmalignant cells in some individuals. They also suggest a mechanistic paradigm for the induction of second malignancies and drug resistance.Keywords
This publication has 18 references indexed in Scilit:
- Deregulated cyclin E induces chromosome instabilityNature, 1999
- Gene mutations with characteristic deletions in cord blood T lymphocytes associated with passive maternal exposure to tobacco smokeNature Medicine, 1998
- Databases and software for the analysis of mutations in the human p53 gene, human hprt gene and both the lacI and lacZ gene in transgenic rodentsNucleic Acids Research, 1998
- Silent and multiple mutations in p53 and the question of the hypermutability of tumors [published erratum appears in Carcinogenesis 1998 Jan;19(1):237]Carcinogenesis: Integrative Cancer Research, 1997
- Gatekeepers and caretakersNature, 1997
- Mutator Specificity and Disease: Looking over the FENceCell, 1997
- SPONTANEOUS MUTATORS IN BACTERIA: Insights into Pathways of Mutagenesis and RepairAnnual Review of Microbiology, 1996
- Determination of hprt mutant frequencies in T-lymphocytes from a healthy pediatric population: statistical comparison between newborn, children and adult mutant frequencies, cloning efficiency and ageMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1994
- Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyltransferase gene in Lesch-Nyhan familiesGenomics, 1990
- Somatic generation of antibody diversityNature, 1983