Interlocus V-J recombination measures genomic instability in agriculture workers at risk for lymphoid malignancies.
V(D)J [variable-(diversity)-joining] rearrangements occur between, as well as within, immune receptor loci, resulting in the generation of hybrid antigen-receptor genes and the formation of a variety of lymphocyte-specific chromosomal aberrations. Such hybrid genes occur at a low frequency in the peripheral blood lymphocytes (PBL) of normal individuals but show a markedly increased incidence in the PBL of individuals with the autosomal recessive disease ataxia-telangiectasia. In this manuscript we demonstrate that the frequency of hybrid antigen-receptor genes is 10- to 20-fold increased in the PBL of an occupational group, agriculture workers, with related environmental exposures. Both ataxia-telangiectasia patients and this population of agriculture workers are at increased risk for lymphoid malignancy. This result suggests that the measurement of hybrid antigen receptor-genes in PBL may be a sensitive assay for a type of lymphocyte-specific genomic instability. As a corollary, this assay may identify populations at risk of developing common types of lymphoid malignancy.
Lipkowitz
S
S
National Cancer Institute-Navy Medical Oncology Branch, Bethesda Naval Hospital, MD 20889-5105.
Garry
V F
VF
Kirsch
I R
IR
D000382:Agricultural Workers' Diseases / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D002897:Chromosomes, Human, Pair 7; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015321:Gene Rearrangement; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008223:Lymphoma / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011995:Recombination, Genetic; D012307:Risk Factors
D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D009838:Oligodeoxyribonucleotides; D011948:Receptors, Antigen, T-Cell; D004247:DNA