Tissue microarray-based screening for chromosomal breakpoints affecting the T-cell receptor gene loci in mature T-cell lymphomas.

The pathogenesis of mature T-cell non-Hodgkin lymphomas (T-NHLs) is poorly understood. Analogous to B-cell lymphomas, in which the immunoglobulin (IgH) receptor loci are frequently targeted by chromosomal translocations, the T-cell receptor (TCR) gene loci are affected by translocations in a subset of precursor T-cell malignancies. In a large-scale analysis of 245 paraffin-embedded mature T-NHLs, arranged in a tissue microarray format and using improved FISH assays for the detection of breakpoints in the TCRalpha/delta, TCRbeta, and TCRgamma loci, we provide evidence that mature T-NHLs other than T-cell prolymphocytic leukaemia (T-PLL) also occasionally show a chromosomal rearrangement that involves the TCRalpha/delta locus. In particular, one peripheral T-cell lymphoma (not otherwise specified, NOS) with the morphological variant of Lennert lymphoma displayed a chromosomal translocation t(14;19) involving the TCRalpha/delta and the BCL3 loci. A second case, an angio-immunoblastic T-cell lymphoma (AILT), carried an inv(14)(q11q32) affecting the TCRalpha/delta and IgH loci. FISH signal constellations as well as concomitant comparative genomic hybridization (CGH) data were also suggestive of the occurrence of an isochromosome 7, previously described to be pathognomonic for hepatosplenic T-cell lymphomas, in rare cases of enteropathy-type T-cell lymphoma.