Neoplasia and chromosomal breakage in ataxia-telangiectasia: a 2:14 translocation

Four common sites of chromosome breakage have been observed in patients with ataxia-telangiectasia (AT): 7p14, 7q35, 14q11.2, and 14q32. These sites appear to coincide with the location of genes for the T-cell receptor subunits (alpha, beta, and gamma) and IGH. Each of these genes involves rearrangements of DNA for its expression, suggesting that an abnormal DNA processing enzyme or family of enzymes underlies this propensity for chromosomal breakage in AT patients. Such a defect could also explain the radiation hypersensitivity of AT fibroblasts. In view of these findings, it is perhaps surprising that AT patients do not manifest more severe immunological defects although they would explain the lack of uniformity of these defects from one patient to the next. Two other genes utilize DNA rearrangement, IGK (on chromosome 2p12) and IGL (on chromosome 22q11), and have not been noted previously to be involved in translocations in these patients. We report here a 2:14 translocation (p14:q32) in a phytohemagglutinin-stimulated lymphocyte from a patient with AT.