Breakage of the T cell receptor alpha chain locus in non malignant clones from patients with ataxia telangiectasia.

Patients with ataxia telangiectasia (A-T) develop specific chromosome translocations, which may confer a proliferative advantage, resulting in the appearance of large clones in the peripheral blood lymphocytes. These lymphocytes are not malignant. Using in situ hybridisation techniques we have investigated a consistent 14q11 translocation breakpoint observed in a t(X;14)(q28;q11) translocation clone from each of two different patients and a t(14;14)(q11;q32) clone from a third patient. In all cases the chromosome translocation involved breakage within the alpha chain locus of the T cell receptor (TCR alpha), between the variable and constant regions, at 14q11. Chromosome rearrangement involving breakage within TCR alpha can therefore precede the development of malignancy. Further chromosomal rearrangement may be required in these patients, for progression to the leukaemic state.