Fragile sites limited to lymphocytes: molecular recombination and malignancy.
Fragile sites on chromosomes are points at which rearrangements tend to occur nonrandomly. Because translocations between chromosomes #7 and #14 occur nonrandomly in normal cultured lymphocytes, we analyzed chromosomes #7 and #14 in 53,580 cultured lymphocytes and 109,300 other human cells. We found one rearrangement per 1,218 lymphocytes. These rearrangements were not restricted to translocations but included inversions and hitherto undetected duplications and deletions. In lymphocytes cultured for only 48 hours, rearrangements were seen indicating their presence in vivo. The breakpoints were exclusively in chromosome bands 7p13, 7q35, 14q11, and 14q32. The predisposition to form these rearrangements appeared nonrandom and inherited. These four bands act as if they contain fragile sites limited to lymphocytes. Fragility was not observed in these bands in cells from amniotic fluid, bone marrow, skin, or chorionic villi. Bands 7p13, 7q35, and 14q11 contain T-cell receptor (TCR) genes, whereas, band 14q32 contains the immunoglobulin heavy (IgH) chain locus. Rearrangements of these bands may result from molecular recombination between TCR or between TCR and IgH genes forming TCR/TCR and TCR/IgH chimeric genes important to understanding lymphocyte development and neoplasia. TCR/IgH chimeric genes have been found in T- and B-cell malignancy.
Hecht
F
F
Hecht
B K
BK
Kirsch
I R
IR
D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002883:Chromosomes, Human, Pair 14; D002897:Chromosomes, Human, Pair 7; D005819:Genetic Markers; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure*; D009369:Neoplasms / Q000235:genetics*; D011995:Recombination, Genetic; D014178:Translocation, Genetic
D005819:Genetic Markers