Characterization of a B-lymphocyte t(2;14) (p11;q32) translocation from an ataxia telangiectasia patient conferring a proliferative advantage on cells in vitro.
Patients with the recessively inherited disorder ataxia telangiectasia (AT) are particularly prone to the development of both B-cell and T-cell tumours. Specific translocations involving T-cell gene rearrangements and an unknown locus 3' of IGH have been described in AT T-cell clone and tumour cells. We describe here a t(2;14)(p11;q32) translocation which was observed in nonmalignant short-term-cultured B lymphocytes from an AT patient. In vivo, the clone of cells grew from 1% to 6% of the total cell population over a period of 2 yr. Clonal translocations may therefore be associated with AT B cells, as well as AT T cells. B lymphocytes were transformed with Epstein-Barr virus, and the t(2;14) translocation cell was cellularly cloned. Using Southern filter analysis and in situ hybridisation to define more clearly the positions of the breakpoints, we show that the translocation at 14q32 involves a deletion within the IGH chain gene of at least J1, J2, DQ52, and sequences 1.5 kb 5' of DQ52 and that the breakpoint is either adjacent to the non-deleted JH sequences or upstream of these sequences, within the D or V regions, but proximal to all members of the VHII family of genes. The breakpoint at 2p11 is outside and proximal to IGK with respect to the centromere in an unknown gene. Sub-lines with an initially low proportion of translocation cells eventually became monoclonal in vitro for these cells. This suggests they have a growth advantage in vitro.
Metcalfe
J A
JA
Department of Cancer Studies, Medical School, University of Birmingham, UK.
Heppell-Parton
A
A
McConville
C M
CM
Taylor
A M
AM
D001260:Ataxia Telangiectasia / Q000235:genetics*; D001402:B-Lymphocytes / Q000648:ultrastructure*; D015139:Blotting, Southern; D002455:Cell Division; D002871:Chromosome Banding; D002883:Chromosomes, Human, Pair 14; D002889:Chromosomes, Human, Pair 2; D002999:Clone Cells; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007621:Karyotyping; D008213:Lymphocyte Activation; D009693:Nucleic Acid Hybridization; D015183:Restriction Mapping; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D007143:Immunoglobulin Heavy Chains